Targeting Microenvironment of Melanoma and Head and Neck Cancers
in Photodynamic Therapy

Ivana       Ratkaj; Martina       Mušković; Nela       Malatesti
Abstract

Background: Photodynamic therapy (PDT), in comparison to other skin cancers, is still far less effective for melanoma, due to the strong absorbance and the role of melanin in cytoprotection. The tumour microenvironment (TME) has a significant role in tumour progression, and the hypoxic TME is one of the main reasons for melanoma progression to metastasis and its resistance to PDT. Hypoxia is also a feature of solid tumours in the head and neck region that indicates negative prognosis.
Objective: The aim of this study was to individuate and describe systematically the main strategies in targeting the TME, especially hypoxia, in PDT against melanoma and head and neck cancers (HNC), and assess the current success in their application.
Methods: PubMed was used for searching, in MEDLINE and other databases, for the most recent publications on PDT against melanoma and HNC in combination with the TME targeting and hypoxia.
Results: In PDT for melanoma and HNC, it is very important to control hypoxia levels, and amongst the different approaches, oxygen self-supply systems are often applied. Vascular targeting is promising, but to improve it, optimal drug-light interval, and formulation to increase the accumulation of the photosensitiser in the tumour vasculature, have to be established. On the other side, the use of angiogenesis inhibitors, such as those interfering with VEGF signalling, is somewhat less successful than expected and needs to be further investigated.
Conclusion: The combination of PDT with immunotherapy by using multifunctional nanoparticles continues to develop and seems to be the most promising for achieving a complete and lasting antitumour effect.
Keywords: Photodynamic therapy, photosensitisers, tumour microenvironment, hypoxia, melanoma, head and neck cancer.
[1] 
Agostinis, P.; Berg, K.; Cengel, K.A.; Foster, T.H.; Girotti, A.W.; Gollnick, S.O.; Hahn, S.M.; Hamblin, M.R.; Juzeniene, A.; Kessel, D.; Korbelik, M.; Moan, J.; Mroz, P.; Nowis, D.; Piette, J.; Wilson, B.C.; Golab, J. Photodynamic therapy of cancer: an update. CA Cancer J. Clin.,  2011, 61(4), 250-281.
[http://dx.doi.org/10.3322/caac.20114] [PMID:  21617154] 
[2] 
Dolmans, D.E.J.G.J.; Fukumura, D.; Jain, R.K. Photodynamic therapy for cancer. Nat. Rev. Cancer,  2003, 3(5), 380-387.
[http://dx.doi.org/10.1038/nrc1071] [PMID:  12724736] 
[3] 
dos Santos, A.F.; de Almeida, D.R.Q.; Terra, L.F.; Baptista, M.S.; Labriola, L. Photodynamic therapy in cancer treatment - an update review. J. Cancer Metastasis Treat.,  2019, 5, 25.
[http://dx.doi.org/10.20517/2394-4722.2018.83] 
[4] 
Gomes, A.T.P.C.; Neves, M.G.P.M.S.; Cavaleiro, J.A.S. Cancer, photodynamic therapy and porphyrin-type derivatives. An. Acad. Bras. Cienc.,  2018, 90(1)(Suppl. 2), 993-1026.
[http://dx.doi.org/10.1590/0001-3765201820170811] [PMID:  29873666] 
[5] 
Benov, L. Photodynamic therapy: current status and future directions. Med. Princ. Pract.,  2015, 24(Suppl. 1), 14-28.
[http://dx.doi.org/10.1159/000362416] [PMID:  24820409] 
[6] 
Engelmann, F.M.; Mayer, I.; Gabrielli, D.S.; Toma, H.E.; Kowaltowski, A.J.; Araki, K.; Baptista, M.S. Interaction of cationic meso-porphyrins with liposomes, mitochondria and erythrocytes. J. Bioenerg. Biomembr.,  2007, 39(2), 175-185.
[http://dx.doi.org/10.1007/s10863-007-9075-0] [PMID:  17436065] 
[7] 
Baptista, M.S.; Cadet, J.; Di Mascio, P.; Ghogare, A.A.; Greer, A.; Hamblin, M.R.; Lorente, C.; Nunez, S.C.; Ribeiro, M.S.; Thomas, A.H.; Vignoni, M.; Yoshimura, T.M. Type I and Type II Photosensitized Oxidation Reactions: Guidelines and Mechanistic Pathways. Photochem. Photobiol.,  2017, 93(4), 912-919.
[http://dx.doi.org/10.1111/php.12716] [PMID:  28084040] 
[8] 
Skovsen, E.; Snyder, J.W.; Lambert, J.D.C.; Ogilby, P.R. Lifetime and diffusion of singlet oxygen in a cell. J. Phys. Chem. B,  2005, 109(18), 8570-8573.
[http://dx.doi.org/10.1021/jp051163i] [PMID:  16852012] 
[9] 
Kessel, D. Photodynamic therapy: a brief history. J. Clin. Med.,  2019, 8(10), 1581.
[http://dx.doi.org/10.3390/jcm8101581] [PMID:  31581613] 
[10] 
Ethirajan, M.; Chen, Y.; Joshi, P.; Pandey, R.K. The role of porphyrin chemistry in tumor imaging and photodynamic therapy. Chem. Soc. Rev.,  2011, 40(1), 340-362.
[http://dx.doi.org/10.1039/B915149B] [PMID:  20694259] 
[11] 
Josefsen, L.B.; Boyle, R.W. Photodynamic therapy and the development of metal-based photosensitisers. Met. Based Drugs,  2008, 2008, 276109.
[http://dx.doi.org/10.1155/2008/276109] [PMID:  18815617] 
[12] 
Josefsen, L.B.; Boyle, R.W. Unique diagnostic and therapeutic roles of porphyrins and phthalocyanines in photodynamic therapy, imaging and theranostics. Theranostics,  2012, 2(9), 916-966.
[http://dx.doi.org/10.7150/thno.4571] [PMID:  23082103] 
[13] 
Abrahamse, H.; Hamblin, M.R. New photosensitizers for photodynamic therapy. Biochem. J.,  2016, 473(4), 347-364.
[http://dx.doi.org/10.1042/BJ20150942] [PMID:  26862179] 
[14] 
Chilakamarthi, U.; Giribabu, L. Photodynamic therapy: past, present and future. Chem. Rec.,  2017, 17(8), 775-802.
[http://dx.doi.org/10.1002/tcr.201600121] [PMID:  28042681] 
[15] 
Castano, A.P.; Demidova, T.N.; Hamblin, M.R. Mechanisms in photodynamic therapy: part one-photosensitizers, photochemistry and cellular localization. Photodiagnosis Photodyn. Ther.,  2004, 1(4), 279-293.
[http://dx.doi.org/10.1016/S1572-1000(05)00007-4] [PMID:  25048432] 
[16] 
Mang, T.S. Lasers and light sources for PDT: Past, present and future. Photodiagnosis Photodyn. Ther.,  2004, 1(1), 43-48.
[17] 
Kim, M.M.; Darafsheh, A. Light sources and dosimetry techniques for photodynamic therapy. Photochem. Photobiol.,  2020, 96(2), 280-294.
[http://dx.doi.org/10.1111/php.13219] [PMID:  32003006] 
[18] 
Postiglione, I.; Chiaviello, A.; Palumbo, G. Enhancing photodynamyc therapy efficacy by combination therapy: dated, current and oncoming strategies. Cancers (Basel),  2011, 3(2), 2597-2629.
[http://dx.doi.org/10.3390/cancers3022597] [PMID:  24212824] 
[19] 
Huang, Z. A review of progress in clinical photodynamic therapy. Technol. Cancer Res. Treat.,  2005, 4(3), 283-293.
[http://dx.doi.org/10.1177/153303460500400308] [PMID:  15896084] 
[20] 
Allison, R.R.; Cuenca, R.E.; Downie, G.H.; Camnitz, P.; Brodish, B.; Sibata, C.H. Clinical photodynamic therapy of head and neck cancers a review of applications and outcomes. Photodiagnosis Photodyn. Ther.,  2005, 2(3), 205-222.
[21] 
Spring, B.Q.; Rizvi, I.; Xu, N.; Hasan, T. The role of photodynamic therapy in overcoming cancer drug resistance. Photochem. Photobiol. Sci.,  2015, 14(8), 1476-1491.
[http://dx.doi.org/10.1039/C4PP00495G] [PMID:  25856800] 
[22] 
Huang, Y-Y.; Vecchio, D.; Avci, P.; Yin, R.; Garcia-Diaz, M.; Hamblin, M.R. Melanoma resistance to photodynamic therapy: new insights. Biol. Chem.,  2013, 394(2), 239-250.
[http://dx.doi.org/10.1515/hsz-2012-0228] [PMID:  23152406] 
[23] 
Eisemann, N.; Waldmann, A.; Geller, A.C.; Weinstock, M.A.; Volkmer, B.; Greinert, R.; Breitbart, E.W.; Katalinic, A. Non-melanoma skin cancer incidence and impact of skin cancer screening on incidence. J. Invest. Dermatol.,  2014, 134(1), 43-50.
[http://dx.doi.org/10.1038/jid.2013.304] [PMID:  23877569] 
[24] 
Samarasinghe, V.; Madan, V.; Lear, J.T. Management of high-risk squamous cell carcinoma of the skin. Expert Rev. Anticancer Ther.,  2011, 11(5), 763-769.
[http://dx.doi.org/10.1586/era.11.36] [PMID:  21554051] 
[25] 
Wong, C.S.M.; Strange, R.C.; Lear, J.T. Basal cell carcinoma. BMJ,  2003, 327(7418), 794-798.
[http://dx.doi.org/10.1136/bmj.327.7418.794] [PMID:  14525881] 
[26] 
Diffey, B.L.; Langtry, J.A.A. Skin cancer incidence and the ageing population. Br. J. Dermatol.,  2005, 679-680.
[27] 
Puig, S.; Berrocal, A. Management of high-risk and advanced basal cell carcinoma. Clin. Transl. Oncol.,  2015, 17(7), 497-503.
[http://dx.doi.org/10.1007/s12094-014-1272-9] [PMID:  25643667] 
[28] 
Cadet, J.; Grand, A.; Douki, T. Photoinduced phenomena in nucleic acids II [Electronic Resource]: DNA fragments and phenomenological aspects. Topics in current chemistry, 356, Springer international publishing.: Cham. 2015.
[29] 
Cadet, J.; Mouret, S.; Ravanat, J-L.; Douki, T. Photoinduced damage to cellular DNA: Direct and photosensitized reactions. Photochem. Photobiol.,  2012, 88(5), 1048-1065.
[http://dx.doi.org/10.1111/j.1751-1097.2012.01200.x] [PMID:  22780837] 
[30] 
Douki, T. The variety of UV-induced pyrimidine dimeric photoproducts in DNA as shown by chromatographic quantification methods. Photochem. Photobiol. Sci.,  2013, 12(8), 1286-1302.
[http://dx.doi.org/10.1039/c3pp25451h] [PMID:  23572060] 
[31] 
Cadet, J.; Douki, T.; Ravanat, J-L. Oxidatively generated damage to cellular DNA by UVB and UVA radiation. Photochem. Photobiol.,  2015, 91(1), 140-155.
[http://dx.doi.org/10.1111/php.12368] [PMID:  25327445] 
[32] 
Justilien, V.; Fields, A.P. Molecular pathways: novel approaches for improved therapeutic targeting of Hedgehog signaling in cancer stem cells. Clin. Cancer Res.,  2015, 21(3), 505-513.
[http://dx.doi.org/10.1158/1078-0432.CCR-14-0507] [PMID:  25646180] 
[33] 
Pellegrini, C.; Maturo, M.G.; Di Nardo, L.; Ciciarelli, V.; Gutiérrez García-Rodrigo, C.; Fargnoli, M.C. Understanding the Molecular Genetics of Basal Cell Carcinoma. Int. J. Mol. Sci.,  2017, 18(11), E2485.
[http://dx.doi.org/10.3390/ijms18112485] [PMID:  29165358] 
[34] 
Katoh, Y.; Katoh, M. Hedgehog target genes: mechanisms of carcinogenesis induced by aberrant hedgehog signaling activation. Curr. Mol. Med.,  2009, 9(7), 873-886.
[http://dx.doi.org/10.2174/156652409789105570] [PMID:  19860666] 
[35] 
Denisova, E.; Heidenreich, B.; Nagore, E.; Rachakonda, P.S.; Hosen, I.; Akrap, I.; Traves, V.; García-Casado, Z.; López-Guerrero, J.A.; Requena, C.; Sanmartin, O.; Serra-Guillén, C.; Llombart, B.; Guillén, C.; Ferrando, J.; Gimeno, E.; Nordheim, A.; Hemminki, K.; Kumar, R. Frequent DPH3 promoter mutations in skin cancers. Oncotarget,  2015, 6(34), 35922-35930.
[http://dx.doi.org/10.18632/oncotarget.5771] [PMID:  26416425] 
[36] 
Röwert-Huber, J.; Patel, M.J.; Forschner, T.; Ulrich, C.; Eberle, J.; Kerl, H.; Sterry, W.; Stockfleth, E. Actinic keratosis is an early in situ squamous cell carcinoma: A proposal for reclassification. Br. J. Dermatol.,  2007, 156(Suppl. 3), 8-12.
[http://dx.doi.org/10.1111/j.1365-2133.2007.07860.x] [PMID:  17488400] 
[37] 
Losquadro, W.D. Anatomy of the skin and the pathogenesis of nonmelanoma skin cancer. Facial Plast. Surg. Clin. North Am.,  2017, 25(3), 283-289.
[http://dx.doi.org/10.1016/j.fsc.2017.03.001] [PMID:  28676156] 
[38] 
Bertolotto, C. Melanoma: From melanocyte to genetic alterations and clinical options. Scientifica (Cairo),  2013, 2013, 635203.
[http://dx.doi.org/10.1155/2013/635203] [PMID:  24416617] 
[39] 
Gray-Schopfer, V.; Wellbrock, C.; Marais, R. Melanoma biology and new targeted therapy. Nature,  2007, 445(7130), 851-857.
[http://dx.doi.org/10.1038/nature05661] [PMID:  17314971] 
[40] 
Lo, J.A.; Fisher, D.E. The melanoma revolution: From uv carcinogenesis to a new era in therapeutics. Science,  2014, (80), 945-949.
[41] 
Alqathama, A. BRAF in malignant melanoma progression and metastasis: Potentials and challenges. Am. J. Cancer Res.,  2020, 10(4), 1103-1114.
[PMID:  32368388] 
[42] 
Fares, J.; Fares, M.Y.; Khachfe, H.H.; Salhab, H.A.; Fares, Y. Molecular principles of metastasis: A hallmark of cancer revisited. Signal Transduct. Target. Ther.,  2020, 5(1), 28.
[http://dx.doi.org/10.1038/s41392-020-0134-x] [PMID:  32296047] 
[43] 
Kirstein, J.M.; Hague, M.N.; McGowan, P.M.; Tuck, A.B.; Chambers, A.F. Primary melanoma tumor inhibits metastasis through alterations in systemic hemostasis. J. Mol. Med. (Berl.),  2016, 94(8), 899-910.
[http://dx.doi.org/10.1007/s00109-016-1415-2] [PMID:  27048169] 
[44] 
Hino, R.; Kabashima, K.; Kato, Y.; Yagi, H.; Nakamura, M.; Honjo, T.; Okazaki, T.; Tokura, Y. Tumor cell expression of programmed cell death-1 ligand 1 is a prognostic factor for malignant melanoma. Cancer,  2010, 116(7), 1757-1766.
[http://dx.doi.org/10.1002/cncr.24899] [PMID:  20143437] 
[45] 
Leach, D.R.; Krummel, M.F.; Allison, J.P. Enhancement of antitumor immunity by CTLA-4 Blockade. Science,  1996, 271, 1734-1736.
[46] 
Chang, W.H.; Lai, A.G. The hypoxic tumour microenvironment: A safe haven for immunosuppressive cells and a therapeutic barrier to overcome. Cancer Lett.,  2020, 487, 34-44.
[http://dx.doi.org/10.1016/j.canlet.2020.05.011] [PMID:  32470490] 
[47] 
Dąbrowski, J.M.; Arnaut, L.G. Photodynamic therapy (PDT) of cancer: From local to systemic treatment. Photochem. Photobiol. Sci.,  2015, 14(10), 1765-1780.
[http://dx.doi.org/10.1039/C5PP00132C] [PMID:  26219737] 
[48] 
Naidoo, C.; Kruger, C.A.; Abrahamse, H. Photodynamic therapy for metastatic melanoma treatment: a review. Technol. Cancer Res. Treat.,  2018, 17, 1533033818791795.
[http://dx.doi.org/10.1177/1533033818791795] [PMID:  30099929] 
[49] 
Sharma, S.K.; Huang, Y-Y.; Hamblin, M.R. Melanoma resistance to photodynamic therapy. Resistance to Photodynamic Therapy in Cancer; Rapozzi, V; Jori, G., Ed.; Springer: Cham, Switzerland, 2015, pp. 229-246.
[http://dx.doi.org/10.1007/978-3-319-12730-9_11] 
[50] 
Baldea, I.; Giurgiu, L.; Teacoe, I.D.; Olteanu, D.E.; Olteanu, F.C.; Clichici, S.; Filip, G.A. Photodynamic therapy in melanoma - Where do we Stand? Curr. Med. Chem.,  2018, 25(40), 5540-5563.
[http://dx.doi.org/10.2174/0929867325666171226115626] [PMID:  29278205] 
[51] 
Cohen, D.K.; Lee, P.K. Photodynamic therapy for non-melanoma skin cancers. Cancers (Basel),  2016, 8(10), 90.
[http://dx.doi.org/10.3390/cancers8100090] [PMID:  27782043] 
[52] 
Baskaran, R.; Lee, J.; Yang, S-G. Clinical development of photodynamic agents and therapeutic applications. Biomater. Res.,  2018, 22, 25.
[http://dx.doi.org/10.1186/s40824-018-0140-z] [PMID:  30275968] 
[53] 
Hamblin, M.R. Photodynamic Therapy for Cancer: What’s Past is Prologue. Photochem. Photobiol.,  2020, 96(3), 506-516.
[http://dx.doi.org/10.1111/php.13190] [PMID:  31820824] 
[54] 
Vera, R.E.; Lamberti, M.J.; Rivarola, V.A.; Rumie Vittar, N.B. Developing strategies to predict photodynamic therapy outcome: The role of melanoma microenvironment. Tumour Biol.,  2015, 36(12), 9127-9136.
[http://dx.doi.org/10.1007/s13277-015-4059-x] [PMID:  26419592] 
[55] 
Ormond, A.B.; Freeman, H.S. Dye sensitizers for photodynamic therapy. Materials (Basel),  2013, 6(3), 817-840.
[http://dx.doi.org/10.3390/ma6030817] [PMID:  28809342] 
[56] 
Milla Sanabria, L.; Rodríguez, M.E.; Cogno, I.S.; Rumie Vittar, N.B.; Pansa, M.F.; Lamberti, M.J.; Rivarola, V.A.; Rivarola, V.A. Direct and indirect photodynamic therapy effects on the cellular and molecular components of the tumor microenvironment. Biochim. Biophys. Acta,  2013, 1835(1), 36-45.
[http://dx.doi.org/10.1016/j.bbcan.2012.10.001] [PMID:  23046998] 
[57] 
Lee, J.T.; Herlyn, M. Microenvironmental influences in melanoma progression. J. Cell. Biochem.,  2007, 101(4), 862-872.
[http://dx.doi.org/10.1002/jcb.21204] [PMID:  17171636] 
[58] 
Wang, P.; Zhang, X.; Sun, N.; Zhao, Z.; He, J. Comprehensive analysis of the tumor microenvironment in cutaneous melanoma associated with immune infiltration. J. Cancer,  2020, 11(13), 3858-3870.
[http://dx.doi.org/10.7150/jca.44413] [PMID:  32328190] 
[59] 
Georgescu, S.R.; Tampa, M.; Mitran, C.I.; Mitran, M.I.; Caruntu, C.; Caruntu, A.; Lupu, M.; Matei, C.; Constantin, C.; Neagu, M. Tumour microenvironment in skin carcinogenesis. Tumour microenvironments in organs: From the brain to the skin – Part A; Birbrair, A., Ed.; Springer International Publishing: Cham, 2020, pp. 123-142.
[http://dx.doi.org/10.1007/978-3-030-36214-0_10] 
[60] 
Sorrin, A.J.; Kemal Ruhi, M.; Ferlic, N.A.; Karimnia, V.; Polacheck, W.J.; Celli, J.P.; Huang, H.C.; Rizvi, I. Photodynamic Therapy and the Biophysics of the Tumor Microenvironment. Photochem. Photobiol.,  2020, 96(2), 232-259.
[http://dx.doi.org/10.1111/php.13209] [PMID:  31895481] 
[61] 
Hsieh, J.C-H.; Wang, H-M.; Wu, M-H.; Chang, K-P.; Chang, P-H.; Liao, C-T.; Liau, C-T. Review of emerging biomarkers in head and neck squamous cell carcinoma in the era of immunotherapy and targeted therapy. Head Neck,  2019, 41(Suppl. 1), 19-45.
[http://dx.doi.org/10.1002/hed.25932] [PMID:  31573749] 
[62] 
Maier, H.; Dietz, A.; Gewelke, U.; Heller, W.D.; Weidauer, H. Tobacco and alcohol and the risk of head and neck cancer. Clin. Investig.,  1992, 70(3-4), 320-327.
[http://dx.doi.org/10.1007/BF00184668] [PMID:  1521046] 
[63] 
Chaturvedi, A.K.; Engels, E.A.; Pfeiffer, R.M.; Hernandez, B.Y.; Xiao, W.; Kim, E.; Jiang, B.; Goodman, M.T.; Sibug-Saber, M.; Cozen, W.; Liu, L.; Lynch, C.F.; Wentzensen, N.; Jordan, R.C.; Altekruse, S.; Anderson, W.F.; Rosenberg, P.S.; Gillison, M.L. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J. Clin. Oncol.,  2011, 29(32), 4294-4301.
[http://dx.doi.org/10.1200/JCO.2011.36.4596] [PMID:  21969503] 
[64] 
Cramer, J.D.; Burtness, B.; Le, Q.T.; Ferris, R.L. The changing therapeutic landscape of head and neck cancer. Nat. Rev. Clin. Oncol.,  2019, 16(11), 669-683.
[http://dx.doi.org/10.1038/s41571-019-0227-z] [PMID:  31189965] 
[65] 
Qiao, X.W.; Jiang, J.; Pang, X.; Huang, M.C.; Tang, Y.J.; Liang, X.H.; Tang, Y.L. The evolving landscape of PD-1/PD-L1 pathway in head and neck cancer. Front. Immunol.,  2020, 11, 1721.
[http://dx.doi.org/10.3389/fimmu.2020.01721] [PMID:  33072064] 
[66] 
Mimikos, C.; Shafirstein, G.; Arshad, H. Current state and future of photodynamic therapy for the treatment of head and neck squamous cell carcinoma. World J. Otorhinolaryngol. Neck Surg.,  2016, 2(2), 126-129.
[67] 
Pucelik, B.; Arnaut, L.G.; Stochel, G.; Dąbrowski, J.M. Design of pluronic-based formulation for enhanced redaporfin-photodynamic therapy against pigmented melanoma. ACS Appl. Mater. Interfaces,  2016, 8(34), 22039-22055.
[http://dx.doi.org/10.1021/acsami.6b07031] [PMID:  27492026] 
[68] 
Meulemans, J.; Delaere, P.; Vander Poorten, V. Photodynamic therapy in head and neck cancer: indications, outcomes, and future prospects. Curr. Opin. Otolaryngol. Head Neck Surg.,  2019, 27(2), 136-141.
[http://dx.doi.org/10.1097/MOO.0000000000000521] [PMID:  30724766] 
[69] 
Senge, M.O.; Brandt, J.C. Temoporfin (Foscan®, 5,10,15,20-tetra(m-hydroxyphenyl)chlorin)--a second-generation photosensitizer. Photochem. Photobiol.,  2011, 87(6), 1240-1296.
[http://dx.doi.org/10.1111/j.1751-1097.2011.00986.x] [PMID:  21848905] 
[70] 
Li, J.Z.; Gao, W.; Chan, J.Y-W.; Ho, W-K.; Wong, T-S. Hypoxia in head and neck squamous cell carcinoma. ISRN Otolaryngol.,  2012, 2012, 708974.
[http://dx.doi.org/10.5402/2012/708974] [PMID:  23762617] 
[71] 
Johnson, D.E.; Burtness, B.; Leemans, C.R.; Lui, V.W.Y.; Bauman, J.E.; Grandis, J.R. Head and neck squamous cell carcinoma. Nat. Rev. Dis. Primers,  2020, 6(1), 92.
[http://dx.doi.org/10.1038/s41572-020-00224-3] [PMID:  33243986] 
[72] 
Bredell, M.G.; Ernst, J.; El-Kochairi, I.; Dahlem, Y.; Ikenberg, K.; Schumann, D.M. Current relevance of hypoxia in head and neck cancer. Oncotarget,  2016, 7(31), 50781-50804.
[http://dx.doi.org/10.18632/oncotarget.9549] [PMID:  27434126] 
[73] 
Joyce, J.A.; Pollard, J.W. Microenvironmental regulation of metastasis. Nat. Rev. Cancer,  2009, 9(4), 239-252.
[http://dx.doi.org/10.1038/nrc2618] [PMID:  19279573] 
[74] 
Balkwill, F.R.; Capasso, M.; Hagemann, T. The tumor microenvironment at a glance. J. Cell Sci.,  2012, 125(Pt 23), 5591-5596.
[http://dx.doi.org/10.1242/jcs.116392] [PMID:  23420197] 
[75] 
Chen, F.; Zhuang, X.; Lin, L.; Yu, P.; Wang, Y.; Shi, Y.; Hu, G.; Sun, Y. New horizons in tumor microenvironment biology: challenges and opportunities. BMC Med.,  2015, 13, 45.
[http://dx.doi.org/10.1186/s12916-015-0278-7] [PMID:  25857315] 
[76] 
Petrova, V.; Annicchiarico-Petruzzelli, M.; Melino, G.; Amelio, I. The hypoxic tumour microenvironment. Oncogenesis,  2018, 7(1), 10.
[http://dx.doi.org/10.1038/s41389-017-0011-9] [PMID:  29362402] 
[77] 
Paolicchi, E.; Gemignani, F.; Krstic-Demonacos, M.; Dedhar, S.; Mutti, L.; Landi, S. Targeting hypoxic response for cancer therapy. Oncotarget,  2016, 7(12), 13464-13478.
[http://dx.doi.org/10.18632/oncotarget.7229] [PMID:  26859576] 
[78] 
Jing, X.; Yang, F.; Shao, C.; Wei, K.; Xie, M.; Shen, H.; Shu, Y. Role of hypoxia in cancer therapy by regulating the tumor microenvironment. Mol. Cancer,  2019, 18(1), 157.
[http://dx.doi.org/10.1186/s12943-019-1089-9] [PMID:  31711497] 
[79] 
Ke, Q.; Costa, M. Hypoxia-inducible Factor-1 (HIF-1). Mol. Pharmacol.,  2006, 70(5), 1469-1480.
[80] 
Wang, G.L.; Jiang, B.H.; Rue, E.A.; Semenza, G.L. Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc. Natl. Acad. Sci. USA,  1995, 92(12), 5510-5514.
[http://dx.doi.org/10.1073/pnas.92.12.5510] [PMID:  7539918] 
[81] 
Tafani, M.; Pucci, B.; Russo, A.; Schito, L.; Pellegrini, L.; Perrone, G.A.; Villanova, L.; Salvatori, L.; Ravenna, L.; Petrangeli, E.; Russo, M.A. Modulators of HIF1α and NFkB in cancer treatment: is it a rational approach for controlling malignant progression? Front. Pharmacol.,  2013, 4, 13.
[http://dx.doi.org/10.3389/fphar.2013.00013] [PMID:  23408731] 
[82] 
Muz, B.; de la Puente, P.; Azab, F.; Azab, A.K. The role of hypoxia in cancer progression, angiogenesis, metastasis, and resistance to therapy. Hypoxia (Auckl.),  2015, 3, 83-92.
[http://dx.doi.org/10.2147/HP.S93413] [PMID:  27774485] 
[83] 
Lv, X.; Li, J.; Zhang, C.; Hu, T.; Li, S.; He, S.; Yan, H.; Tan, Y.; Lei, M.; Wen, M.; Zuo, J. The role of hypoxia-inducible factors in tumor angiogenesis and cell metabolism. Genes Dis.,  2016, 4(1), 19-24.
[http://dx.doi.org/10.1016/j.gendis.2016.11.003] [PMID:  30258904] 
[84] 
Hill, R.P.; Marie-Egyptienne, D.T.; Hedley, D.W. Cancer stem cells, hypoxia and metastasis. Semin. Radiat. Oncol.,  2009, 19(2), 106-111.
[http://dx.doi.org/10.1016/j.semradonc.2008.12.002] [PMID:  19249648] 
[85] 
Olcina, M.M.; Kim, R.K.; Melemenidis, S.; Graves, E.E.; Giaccia, A.J. The tumour microenvironment links complement system dysregulation and hypoxic signalling. Br. J. Radiol.,  2019, 92(1093), 20180069.
[http://dx.doi.org/10.1259/bjr.20180069] [PMID:  29544344] 
[86] 
Cirri, P.; Chiarugi, P. Cancer-associated-fibroblasts and tumour cells: a diabolic liaison driving cancer progression. Cancer Metastasis Rev.,  2012, 31(1-2), 195-208.
[http://dx.doi.org/10.1007/s10555-011-9340-x] [PMID:  22101652] 
[87] 
Tao, L.; Huang, G.; Song, H.; Chen, Y.; Chen, L. Cancer associated fibroblasts: An essential role in the tumor microenvironment. Oncol. Lett.,  2017, 14(3), 2611-2620.
[http://dx.doi.org/10.3892/ol.2017.6497] [PMID:  28927027] 
[88] 
Roma-Rodrigues, C.; Mendes, R.; Baptista, P.V.; Fernandes, A.R. Targeting tumor microenvironment for cancer therapy. Int. J. Mol. Sci.,  2019, 20(4), E840.
[http://dx.doi.org/10.3390/ijms20040840] [PMID:  30781344] 
[89] 
Barsoum, I.B.; Smallwood, C.A.; Siemens, D.R.; Graham, C.H. A mechanism of hypoxia-mediated escape from adaptive immunity in cancer cells. Cancer Res.,  2014, 74(3), 665-674.
[http://dx.doi.org/10.1158/0008-5472.CAN-13-0992] [PMID:  24336068] 
[90] 
Noman, M.Z.; Desantis, G.; Janji, B.; Hasmim, M.; Karray, S.; Dessen, P.; Bronte, V.; Chouaib, S. PD-L1 is a novel direct target of HIF-1α, and its blockade under hypoxia enhanced MDSC-mediated T cell activation. J. Exp. Med.,  2014, 211(5), 781-790.
[http://dx.doi.org/10.1084/jem.20131916] [PMID:  24778419] 
[91] 
Dang, J.; He, H.; Chen, D.; Yin, L. Manipulating tumor hypoxia toward enhanced photodynamic therapy (PDT). Biomater. Sci.,  2017, 5(8), 1500-1511.
[http://dx.doi.org/10.1039/C7BM00392G] [PMID:  28681887] 
[92] 
Li, X.; Kwon, N.; Guo, T.; Liu, Z.; Yoon, J. Innovative strategies for hypoxic-tumor photodynamic therapy. Angew. Chem. Int. Ed. Engl.,  2018, 57(36), 11522-11531.
[http://dx.doi.org/10.1002/anie.201805138] [PMID:  29808948] 
[93] 
Callaghan, S.; Senge, M.O. The good, the bad, and the ugly - controlling singlet oxygen through design of photosensitizers and delivery systems for photodynamic therapy. Photochem. Photobiol. Sci.,  2018, 17(11), 1490-1514.
[http://dx.doi.org/10.1039/C8PP00008E] [PMID:  29569665] 
[94] 
Larue, L.; Myrzakhmetov, B.; Ben-Mihoub, A.; Moussaron, A.; Thomas, N.; Arnoux, P.; Baros, F.; Vanderesse, R.; Acherar, S.; Frochot, C. Fighting hypoxia to improve PDT. Pharmaceuticals (Basel),  2019, 12(4), 1-115.
[http://dx.doi.org/10.3390/ph12040163] [PMID:  31671658] 
[95] 
Corbet, C.; Feron, O. Tumour acidosis: from the passenger to the driver’s seat. Nat. Rev. Cancer,  2017, 17(10), 577-593.
[http://dx.doi.org/10.1038/nrc.2017.77] [PMID:  28912578] 
[96] 
Dong, Y.; Tu, Y.; Wang, K.; Xu, C.; Yuan, Y.; Wang, J. A general strategy for macrotheranostic prodrug activation: Synergy between the acidic tumor microenvironment and bioorthogonal chemistry. Angew. Chem. Int. Ed. Engl.,  2020, 59(18), 7168-7172.
[http://dx.doi.org/10.1002/anie.201913522] [PMID:  32003112] 
[97] 
Wang, C.; Zhao, P.; Yang, G.; Chen, X.; Jiang, Y.; Jiang, X.; Wu, Y.; Liu, Y.; Zhang, W.; Bu, W. Reconstructing the intracellular PH microenvironment for enhancing photodynamic therapy. Mater. Horiz.,  2020, 7(4), 1180-1185.
[http://dx.doi.org/10.1039/C9MH01824G] 
[98] 
Lamberti, M.J.; Morales Vasconsuelo, A.B.; Ferrara, M.G.; Rumie Vittar, N.B. Recapitulation of hypoxic tumor-stroma microenvironment to study photodynamic therapy implications. Photochem. Photobiol.,  2020, 96(4), 897-905.
[http://dx.doi.org/10.1111/php.13220] [PMID:  32012283] 
[99] 
Ji, Z.; Yang, G.; Shahzidi, S.; Tkacz-Stachowska, K.; Suo, Z.; Nesland, J.M.; Peng, Q. Induction of hypoxia-inducible factor-1alpha overexpression by cobalt chloride enhances cellular resistance to photodynamic therapy. Cancer Lett.,  2006, 244(2), 182-189.
[http://dx.doi.org/10.1016/j.canlet.2005.12.010] [PMID:  16427735] 
[100] 
Jiang, L.; Liu, L.; Lv, F.; Wang, S.; Ren, X. Integration of self-luminescence and oxygen self-supply: a potential photodynamic therapy strategy for deep tumor treatment. ChemPlusChem,  2020, 85(3), 510-518.
[http://dx.doi.org/10.1002/cplu.202000083] [PMID:  32187852] 
[101] 
Rui, X.; Yang, Y.; Wu, J.; Chen, J.; Chen, Q.; Ren, R.; Zhang, Q.; Hu, Y.; Yin, D. Multi-path tumor inhibition via the interactive effects between tumor microenvironment and an oxygen self-supplying delivery system for a photosensitizer. Photodiagnosis Photodyn. Ther.,  2020, 29, 101642.
[http://dx.doi.org/10.1016/j.pdpdt.2019.101642] [PMID:  31899380] 
[102] 
Malatesti, N.; Munitic, I.; Jurak, I. Porphyrin-based cationic amphiphilic photosensitisers as potential anticancer, antimicrobial and immunosuppressive agents. Biophys. Rev.,  2017, 9(2), 149-168.
[http://dx.doi.org/10.1007/s12551-017-0257-7] [PMID:  28510089] 
[103] 
Garg, A.D.; Nowis, D.; Golab, J.; Agostinis, P. Photodynamic therapy: illuminating the road from cell death towards anti-tumour immunity. Apoptosis,  2010, 15(9), 1050-1071.
[http://dx.doi.org/10.1007/s10495-010-0479-7] [PMID:  20221698] 
[104] 
Sivasubramanian, M.; Chuang, Y.C.; Lo, L-W. Evolution of nanoparticle-mediated photodynamic therapy: from superficial to deep-seated cancers. Molecules,  2019, 24(3), 520.
[http://dx.doi.org/10.3390/molecules24030520] [PMID:  30709030] 
[105] 
Mfouo Tynga, I.; Abrahamse, H. Nano-mediated photodynamic therapy for cancer: enhancement of cancer specificity and therapeutic effects. Nanomaterials (Basel),  2018, 8(11), 923.
[http://dx.doi.org/10.3390/nano8110923] [PMID:  30412991] 
[106] 
Chizenga, E.P.; Abrahamse, H. Nanotechnology in modern photodynamic therapy of cancer: a review of cellular resistance patterns affecting the therapeutic response. Pharmaceutics,  2020, 12(7), E632.
[http://dx.doi.org/10.3390/pharmaceutics12070632] [PMID:  32640564] 
[107] 
Pedziwiatr-Werbicka, E.; Horodecka, K.; Shcharbin, D.; Bryszewska, M. Nanoparticles in combating cancer: opportunities and limitations. a brief review. Curr. Med. Chem.,  2021, 28(2), 346-359.
[http://dx.doi.org/10.2174/0929867327666200130101605] [PMID:  32000637] 
[108] 
Quirk, B.J.; Brandal, G.; Donlon, S.; Vera, J.C.; Mang, T.S.; Foy, A.B.; Lew, S.M.; Girotti, A.W.; Jogal, S.; LaViolette, P.S.; Connelly, J.M.; Whelan, H.T. Photodynamic therapy (PDT) for malignant brain tumors--where do we stand? Photodiagnosis Photodyn. Ther.,  2015, 12(3), 530-544.
[http://dx.doi.org/10.1016/j.pdpdt.2015.04.009] [PMID:  25960361] 
[109] 
Pucelik, B.; Sułek, A.; Dąbrowski, J.M. Bacteriochlorins and their metal complexes as NIR-absorbing photosensitizers: properties, mechanisms, and applications. Coord. Chem. Rev.,  2020, 416, 213340.
[http://dx.doi.org/10.1016/j.ccr.2020.213340] 
[110] 
Sheleg, S.V.; Zhavrid, E.A.; Khodina, T.V.; Kochubeev, G.A.; Istomin, Y.P.; Chalov, V.N.; Zhuravkin, I.N. Photodynamic therapy with chlorin e(6) for skin metastases of melanoma. Photodermatol. Photoimmunol. Photomed.,  2004, 20(1), 21-26.
[http://dx.doi.org/10.1111/j.1600-0781.2004.00078.x] [PMID:  14738529] 
[111] 
Pires, L.; Demidov, V.; Wilson, B.C.; Salvio, A.G.; Moriyama, L.; Bagnato, V.S.; Vitkin, I.A.; Kurachi, C. Dual-agent photodynamic therapy with optical clearing eradicates pigmented melanoma in preclinical tumor models. Cancers (Basel),  2020, 12(7), 1956.
[http://dx.doi.org/10.3390/cancers12071956] [PMID:  32708501] 
[112] 
Tahmasebi, H.; Khoshgard, K.; Sazgarnia, A.; Mostafaie, A.; Eivazi, M.T. Enhancing the efficiency of 5-aminolevulinic acid-mediated photodynamic therapy using 5-fluorouracil on human melanoma cells. Photodiagnosis Photodyn. Ther.,  2016, 13, 297-302.
[http://dx.doi.org/10.1016/j.pdpdt.2015.08.011] [PMID:  26321747] 
[113] 
Leviskas, B.; Valyi-Nagy, T.; Munirathinam, G.; Bork, M.; Valyi-Nagy, K.; Skwor, T. Metalloporphyrin Pd(T4) exhibits oncolytic activity and cumulative effects with 5-ALA photodynamic treatment against C918 cells. Int. J. Mol. Sci.,  2020, 21(2), E669.
[http://dx.doi.org/10.3390/ijms21020669] [PMID:  31968535] 
[114] 
Tao, Y-K.; Hou, X-Y.; Gao, H.; Zhang, X.; Zuo, F-M.; Wang, Y.; Li, X-X.; Jiang, G. Grade-targeted nanoparticles for improved hypoxic tumor microenvironment and enhanced photodynamic cancer therapy. Nanomedicine (Lond.),  2021, 16(3), 221-235.
[http://dx.doi.org/10.2217/nnm-2020-0096] [PMID:  33533660] 
[115] 
Shi, Y.; van der Meel, R.; Chen, X.; Lammers, T. The EPR effect and beyond: Strategies to improve tumor targeting and cancer nanomedicine treatment efficacy. Theranostics,  2020, 10(17), 7921-7924.
[http://dx.doi.org/10.7150/thno.49577] [PMID:  32685029] 
[116] 
Zheng, Y.; Ye, J.; Li, Z.; Chen, H.; Gao, Y. Recent progress in sono-photodynamic cancer therapy: from developed new sensitizers to nanotechnology-based efficacy enhancing strategies. Acta Pharm. Sin. B, 2020.
[117] 
Goto, P.L.; Siqueira-Moura, M.P.; Tedesco, A.C. Application of aluminum chloride phthalocyanine-loaded solid lipid nanoparticles for photodynamic inactivation of melanoma cells. Int. J. Pharm.,  2017, 518(1-2), 228-241.
[http://dx.doi.org/10.1016/j.ijpharm.2017.01.004] [PMID:  28063902] 
[118] 
do Reis, S.R.R.; Helal-Neto, E.; da Silva de Barros, A.O.; Pinto, S.R.; Portilho, F.L.; de Oliveira Siqueira, L.B.; Alencar, L.M.R.; Dahoumane, S.A.; Alexis, F.; Ricci-Junior, E.; Santos-Oliveira, R. Dual encapsulated dacarbazine and zinc phthalocyanine polymeric nanoparticle for photodynamic therapy of melanoma. Pharm. Res.,  2021, 38(2), 335-346.
[http://dx.doi.org/10.1007/s11095-021-02999-w] [PMID:  33604784] 
[119] 
Valli, F.; García Vior, M.C.; Roguin, L.P.; Marino, J. Crosstalk between oxidative stress-induced apoptotic and autophagic signaling pathways in Zn(II) phthalocyanine photodynamic therapy of melanoma. Free Radic. Biol. Med.,  2020, 152, 743-754.
[http://dx.doi.org/10.1016/j.freeradbiomed.2020.01.018] [PMID:  31962157] 
[120] 
Ouyang, X.; Wang, X.; Kraatz, H-B.; Ahmadi, S.; Gao, J.; Lv, Y.; Sun, X.; Huang, Y. A Trojan horse biomimetic delivery strategy using mesenchymal stem cells for PDT/PTT therapy against lung melanoma metastasis. Biomater. Sci.,  2020, 8(4), 1160-1170.
[http://dx.doi.org/10.1039/C9BM01401B] [PMID:  31848537] 
[121] 
Rapozzi, V.; Zorzet, S.; Zacchigna, M.; Drioli, S.; Xodo, L.E. The PDT activity of free and pegylated pheophorbide a against an amelanotic melanoma transplanted in C57/BL6 mice. Invest. New Drugs,  2013, 31(1), 192-199.
[http://dx.doi.org/10.1007/s10637-012-9844-4] [PMID:  22688292] 
[122] 
Clemente, N.; Miletto, I.; Gianotti, E.; Invernizzi, M.; Marchese, L.; Dianzani, U.; Renò, F. Verteporfin-loaded mesoporous silica nanoparticles inhibit mouse melanoma proliferation in vitro and in vivo. J. Photochem. Photobiol. B,  2019, 197, 111533.
[http://dx.doi.org/10.1016/j.jphotobiol.2019.111533] [PMID:  31254952] 
[123] 
Mohammadalipour, Z.; Rahmati, M.; Khataee, A.; Moosavi, M.A. Differential effects of N-TiO2 nanoparticle and its photo-activated form on autophagy and necroptosis in human melanoma A375 cells. J. Cell. Physiol.,  2020, 235(11), 8246-8259.
[http://dx.doi.org/10.1002/jcp.29479] [PMID:  31989650] 
[124] 
Wei, C.; Li, X. The role of photoactivated and non-photoactivated verteporfin on tumor. Front. Pharmacol.,  2020, 11, 557429.
[http://dx.doi.org/10.3389/fphar.2020.557429] [PMID:  33178014] 
[125] 
Weiss, A.; den Bergh, Hv.; Griffioen, A.W.; Nowak-Sliwinska, P. Angiogenesis inhibition for the improvement of photodynamic therapy: the revival of a promising idea. Biochim. Biophys. Acta,  2012, 1826(1), 53-70.
[http://dx.doi.org/10.1016/j.bbcan.2012.03.003] [PMID:  22465396] 
[126] 
Camerin, M.; Magaraggia, M.; Soncin, M.; Jori, G.; Moreno, M.; Chambrier, I.; Cook, M.J.; Russell, D.A. The in vivo efficacy of phthalocyanine-nanoparticle conjugates for the photodynamic therapy of amelanotic melanoma. Eur. J. Cancer,  2010, 46(10), 1910-1918.
[http://dx.doi.org/10.1016/j.ejca.2010.02.037] [PMID:  20356732] 
[127] 
Krzykawska-Serda, M.; Dąbrowski, J.M.; Arnaut, L.G.; Szczygieł, M.; Urbańska, K.; Stochel, G.; Elas, M. The role of strong hypoxia in tumors after treatment in the outcome of bacteriochlorin-based photodynamic therapy. Free Radic. Biol. Med.,  2014, 73, 239-251.
[http://dx.doi.org/10.1016/j.freeradbiomed.2014.05.003] [PMID:  24835769] 
[128] 
Zilberstein, J.; Schreiber, S.; Bloemers, M.C.; Bendel, P.; Neeman, M.; Schechtman, E.; Kohen, F.; Scherz, A.; Salomon, Y. Antivascular treatment of solid melanoma tumors with bacteriochlorophyll-serine-based photodynamic therapy. Photochem. Photobiol.,  2001, 73(3), 257-266.
[http://dx.doi.org/10.1562/0031-8655(2001)073<0257:ATOSMT>2.0.CO;2] [PMID:  11281022] 
[129] 
Lu, Z.; Jia, W.; Deng, R.; Zhou, Y.; Li, X.; Yu, T.; Zhen, M.; Wang, C. Light-assisted gadofullerene nanoparticles disrupt tumor vasculatures for potent melanoma treatment. J. Mater. Chem. B Mater. Biol. Med.,  2020, 8(12), 2508-2518.
[http://dx.doi.org/10.1039/C9TB02752A] [PMID:  32124888] 
[130] 
Lee, C-H.; Lai, P-S.; Lu, Y-P.; Chen, H-Y.; Chai, C-Y.; Tsai, R-K.; Fang, K-T.; Tsai, M-H.; Hsu, C-Y.; Hung, C-C.; Wu, D.C.; Yu, H.S.; Chang, C.H.; Tsai, D.P. Real-time vascular imaging and photodynamic therapy efficacy with micelle-nanocarrier delivery of chlorin e6 to the microenvironment of melanoma. J. Dermatol. Sci.,  2015, 80(2), 124-132.
[http://dx.doi.org/10.1016/j.jdermsci.2015.08.005] [PMID:  26360010] 
[131] 
Tammela, T.; Saaristo, A.; Holopainen, T.; Ylä-Herttuala, S.; Andersson, L.C.; Virolainen, S.; Immonen, I.; Alitalo, K. Photodynamic ablation of lymphatic vessels and intralymphatic cancer cells prevents metastasis. Sci. Transl. Med.,  2011, 3(69), 69ra11.
[http://dx.doi.org/10.1126/scitranslmed.3001699] [PMID:  21307301] 
[132] 
Li, J.; Xue, Y.; Tian, J.; Liu, Z.; Zhuang, A.; Gu, P.; Zhou, H.; Zhang, W.; Fan, X. Fluorinated-functionalized hyaluronic acid nanoparticles for enhanced photodynamic therapy of ocular choroidal melanoma by ameliorating hypoxia. Carbohydr. Polym.,  2020, 237, 116119.
[http://dx.doi.org/10.1016/j.carbpol.2020.116119] [PMID:  32241431] 
[133] 
Zhou, J.; Geng, S.; Ye, W.; Wang, Q.; Lou, R.; Yin, Q.; Du, B.; Yao, H. ROS-boosted photodynamic therapy against metastatic melanoma by inhibiting the activity of antioxidase and oxygen-producing nano-dopants. Pharmacol. Res.,  2020, 158, 104885.
[http://dx.doi.org/10.1016/j.phrs.2020.104885] [PMID:  32434051] 
[134] 
Wen, L.; Hyoju, R.; Wang, P.; Shi, L.; Li, C.; Li, M.; Wang, X. Hydrogen-peroxide-responsive protein biomimetic nanoparticles for photothermal-photodynamic combination therapy of melanoma. Lasers Surg. Med., 2020.
[http://dx.doi.org/10.1002/lsm.23292] [PMID:  32596824] 
[135] 
Hou, X.; Tao, Y.; Li, X.; Pang, Y.; Yang, C.; Jiang, G.; Liu, Y. CD44-targeting oxygen self-sufficient nanoparticles for enhanced photodynamic therapy against malignant melanoma. Int. J. Nanomedicine,  2020, 15, 10401-10416.
[http://dx.doi.org/10.2147/IJN.S283515] [PMID:  33376328] 
[136] 
Zhang, Z.; Wang, R.; Huang, X.; Luo, R.; Xue, J.; Gao, J.; Liu, W.; Liu, F.; Feng, F.; Qu, W. Self-delivered and self-monitored chemo-photodynamic nanoparticles with light-triggered synergistic antitumor therapies by downregulation of HIF-1α and depletion of GSH. ACS Appl. Mater. Interfaces,  2020, 12(5), 5680-5694.
[http://dx.doi.org/10.1021/acsami.9b23325] [PMID:  31944660] 
[137] 
Hwang, H.S.; Cherukula, K.; Bang, Y.J.; Vijayan, V.; Moon, M.J.; Thiruppathi, J.; Puth, S.; Jeong, Y.Y.; Park, I-K.; Lee, S.E.; Rhee, J.H. Combination of photodynamic therapy and a flagellin-adjuvanted cancer vaccine potentiated the anti-PD-1-mediated melanoma suppression. Cells,  2020, 9(11), E2432.
[http://dx.doi.org/10.3390/cells9112432] [PMID:  33171765] 
[138] 
Oh, D.S.; Kim, H.; Oh, J.E.; Jung, H.E.; Lee, Y.S.; Park, J-H.; Lee, H.K. Intratumoral depletion of regulatory T cells using CD25-targeted photodynamic therapy in a mouse melanoma model induces antitumoral immune responses. Oncotarget,  2017, 8(29), 47440-47453.
[http://dx.doi.org/10.18632/oncotarget.17663] [PMID:  28537894] 
[139] 
Kaliki, S.; Shields, C.L. Uveal melanoma: relatively rare but deadly cancer. Eye (Lond.),  2017, 31(2), 241-257.
[http://dx.doi.org/10.1038/eye.2016.275] [PMID:  27911450] 
[140] 
Kim, S.; Kim, S.A.; Nam, G-H.; Hong, Y.; Kim, G.B.; Choi, Y.; Lee, S.; Cho, Y.; Kwon, M.; Jeong, C.; Kim, S.; Kim, I.S. in situ immunogenic clearance induced by a combination of photodynamic therapy and rho-kinase inhibition sensitizes immune checkpoint blockade response to elicit systemic antitumor immunity against intraocular melanoma and its metastasis. J. Immunother. Cancer,  2021, 9(1), e001481.
[http://dx.doi.org/10.1136/jitc-2020-001481] [PMID:  33479026] 
[141] 
Yang, W.; Zhang, F.; Deng, H.; Lin, L.; Wang, S.; Kang, F.; Yu, G.; Lau, J.; Tian, R.; Zhang, M.; Wang, Z.; He, L.; Ma, Y.; Niu, G.; Hu, S.; Chen, X. Smart nanovesicle-mediated immunogenic cell death through tumor microenvironment modulation for effective photodynamic immunotherapy. ACS Nano,  2020, 14(1), 620-631.
[http://dx.doi.org/10.1021/acsnano.9b07212] [PMID:  31877023] 
[142] 
Kim, D.; Byun, J.; Park, J.; Lee, Y.; Shim, G.; Oh, Y-K. Biomimetic polymeric nanoparticle-based photodynamic immunotherapy and protection against tumor rechallenge. Biomater. Sci.,  2020, 8(4), 1106-1116.
[http://dx.doi.org/10.1039/C9BM01704F] [PMID:  31994549] 
[143] 
Wen, A.M.; Lee, K.L.; Cao, P.; Pangilinan, K.; Carpenter, B.L.; Lam, P.; Veliz, F.A.; Ghiladi, R.A.; Advincula, R.C.; Steinmetz, N.F. Utilizing viral nanoparticle/dendron hybrid conjugates in photodynamic therapy for dual delivery to macrophages and cancer cells. Bioconjug. Chem.,  2016, 27(5), 1227-1235.
[http://dx.doi.org/10.1021/acs.bioconjchem.6b00075] [PMID:  27077475] 
[144] 
Ai, X.; Hu, M.; Wang, Z.; Lyu, L.; Zhang, W.; Li, J.; Yang, H.; Lin, J.; Xing, B. Enhanced cellular ablation by attenuating hypoxia status and reprogramming tumor-associated macrophages via NIR light-responsive upconversion nanocrystals. Bioconjug. Chem.,  2018, 29(4), 928-938.
[http://dx.doi.org/10.1021/acs.bioconjchem.8b00068] [PMID:  29466856] 
[145] 
Kleemann, B.; Loos, B.; Scriba, T.J.; Lang, D.; Davids, L.M. St John’s Wort (Hypericum perforatum L.) photomedicine: Hypericin-photodynamic therapy induces metastatic melanoma cell death. PLoS One,  2014, 9(7), e103762.
[http://dx.doi.org/10.1371/journal.pone.0103762] [PMID:  25076130] 
[146] 
Popovic, A.; Wiggins, T.; Davids, L.M. Differential susceptibility of primary cultured human skin cells to hypericin PDT in an in vitro model. J. Photochem. Photobiol. B,  2015, 149, 249-256.
[http://dx.doi.org/10.1016/j.jphotobiol.2015.06.009] [PMID:  26114219] 
[147] 
Wagner, M.; Suarez, E.R.; Theodoro, T.R.; Machado Filho, C.D.A.S.; Gama, M.F.M.; Tardivo, J.P.; Paschoal, F.M.; Pinhal, M.A.S. Methylene blue photodynamic therapy in malignant melanoma decreases expression of proliferating cell nuclear antigen and heparanases. Clin. Exp. Dermatol.,  2012, 37(5), 527-533.
[http://dx.doi.org/10.1111/j.1365-2230.2011.04291.x] [PMID:  22299594] 
[148] 
Chen, Y.; Zheng, W.; Li, Y.; Zhong, J.; Ji, J.; Shen, P. Apoptosis induced by methylene-blue-mediated photodynamic therapy in melanomas and the involvement of mitochondrial dysfunction revealed by proteomics. Cancer Sci.,  2008, 99(10), 2019-2027.
[http://dx.doi.org/10.1111/j.1349-7006.2008.00910.x] [PMID:  19016762] 
[149] 
Dhillon, S.K.; Porter, S.L.; Rizk, N.; Sheng, Y.; McKaig, T.; Burnett, K.; White, B.; Nesbitt, H.; Matin, R.N.; McHale, A.P.; Callan, B.; Callan, J.F. Rose bengal-amphiphilic peptide conjugate for enhanced photodynamic therapy of malignant melanoma. J. Med. Chem.,  2020, 63(3), 1328-1336.
[http://dx.doi.org/10.1021/acs.jmedchem.9b01802] [PMID:  31940202] 
[150] 
Ng, S.Y.; Kamkaew, A.; Fu, N.; Kue, C.S.; Chung, L.Y.; Kiew, L.V.; Wittayakun, J.; Burgess, K.; Lee, H.B. Active targeted ligand-aza-BODIPY conjugate for near-infrared photodynamic therapy in melanoma. Int. J. Pharm.,  2020, 579, 119189.
[http://dx.doi.org/10.1016/j.ijpharm.2020.119189] [PMID:  32126251] 
[151] 
Wolnicka-Glubisz, A.; Pawlak, A.; Insinska-Rak, M.; Zadlo, A. Analysis of photoreactivity and phototoxicity of riboflavin’s analogue 3MeTARF. J. Photochem. Photobiol. B,  2020, 205, 111820.
[http://dx.doi.org/10.1016/j.jphotobiol.2020.111820] [PMID:  32065959] 
[152] 
Akasov, R.A.; Sholina, N.V.; Khochenkov, D.A.; Alova, A.V.; Gorelkin, P.V.; Erofeev, A.S.; Generalova, A.N.; Khaydukov, E.V. Photodynamic therapy of melanoma by blue-light photoactivation of flavin mononucleotide. Sci. Rep.,  2019, 9(1), 9679.
[http://dx.doi.org/10.1038/s41598-019-46115-w] [PMID:  31273268] 
[153] 
Hosokawa, S.; Takebayashi, S.; Takahashi, G.; Okamura, J.; Mineta, H. Photodynamic therapy in patients with head and neck squamous cell carcinoma. Lasers Surg. Med.,  2018, 50(5), 420-426.
[http://dx.doi.org/10.1002/lsm.22802] [PMID:  29399863] 
[154] 
Mallidi, S.; Anbil, S.; Bulin, A-L.; Obaid, G.; Ichikawa, M.; Hasan, T. beyond the barriers of light penetration: strategies, perspectives and possibilities for photodynamic therapy. Theranostics,  2016, 6(13), 2458-2487.
[http://dx.doi.org/10.7150/thno.16183] [PMID:  27877247] 
[155] 
Yakavets, I.; Jenard, S.; Francois, A.; Maklygina, Y.; Loschenov, V.; Lassalle, H-P.; Dolivet, G.; Bezdetnaya, L. Stroma-rich co-culture multicellular tumor spheroids as a tool for photoactive drugs screening. J. Clin. Med.,  2019, 8(10), 1686.
[http://dx.doi.org/10.3390/jcm8101686] [PMID:  31618880] 
[156] 
Yakavets, I.; Francois, A.; Lamy, L.; Piffoux, M.; Gazeau, F.; Wilhelm, C.; Zorin, V.; Silva, A.K.A.; Bezdetnaya, L. Effect of stroma on the behavior of temoporfin-loaded lipid nanovesicles inside the stroma-rich head and neck carcinoma spheroids. J. Nanobiotechnology,  2021, 19(1), 3.
[http://dx.doi.org/10.1186/s12951-020-00743-x] [PMID:  33407564] 
[157] 
Anand, S.; Honari, G.; Hasan, T.; Elson, P.; Maytin, E.V. Low-dose methotrexate enhances aminolevulinate-based photodynamic therapy in skin carcinoma cells in vitro and in vivo. Clin. Cancer Res.,  2009, 15(10), 3333-3343.
[http://dx.doi.org/10.1158/1078-0432.CCR-08-3054] [PMID:  19447864] 
[158] 
Anand, S.; Wilson, C.; Hasan, T.; Maytin, E.V. Vitamin D3 enhances the apoptotic response of epithelial tumors to aminolevulinate-based photodynamic therapy. Cancer Res.,  2011, 71(18), 6040-6050.
[http://dx.doi.org/10.1158/0008-5472.CAN-11-0805] [PMID:  21807844] 
[159] 
Anand, S.; Rollakanti, K.R.; Horst, R.L.; Hasan, T.; Maytin, E.V. Combination of oral vitamin D3 with photodynamic therapy enhances tumor cell death in a murine model of cutaneous squamous cell carcinoma. Photochem. Photobiol.,  2014, 90(5), 1126-1135.
[http://dx.doi.org/10.1111/php.12286] [PMID:  24807677] 
[160] 
León, D.; Buchegger, K.; Silva, R.; Riquelme, I.; Viscarra, T.; Mora-Lagos, B.; Zanella, L.; Schafer, F.; Kurachi, C.; Roa, J.C.; Ili, C.; Brebi, P. Epigallocatechin gallate enhances MAL-PDT cytotoxic effect on PDT-resistant skin cancer squamous cells. Int. J. Mol. Sci.,  2020, 21(9), E3327.
[http://dx.doi.org/10.3390/ijms21093327] [PMID:  32397263] 
[161] 
Li, S.; Wang, P.; Zhang, G.; Ji, J.; Lv, T.; Wang, X.; Wang, H. The effect of ALA-PDT on reversing the activation of cancer-associated fibroblasts in cutaneous squamous cell carcinoma. Photodiagnosis Photodyn. Ther.,  2019, 27, 234-240.
[http://dx.doi.org/10.1016/j.pdpdt.2019.05.043] [PMID:  31163284] 
[162] 
Zhu, L.; Zhang, G.; Wang, P.; Zhang, L.; Ji, J.; Liu, X.; Zhou, Z.; Zhao, J.; Wang, X. The effect of C-X-C motif chemokine ligand 13 in cutaneous squamous cell carcinoma treated with aminolevulinic acid-photodynamic therapy. Photodiagnosis Photodyn. Ther.,  2019, 26, 389-394.
[http://dx.doi.org/10.1016/j.pdpdt.2019.04.018] [PMID:  31022580] 
[163] 
Ahn, P.H.; Finlay, J.C.; Gallagher-Colombo, S.M.; Quon, H.; O’Malley, B.W.J., Jr; Weinstein, G.S.; Chalian, A.; Malloy, K.; Sollecito, T.; Greenberg, M.; Simone, C.B., II; McNulty, S.; Lin, A.; Zhu, T.C.; Livolsi, V.; Feldman, M.; Mick, R.; Cengel, K.A.; Busch, T.M. Lesion oxygenation associates with clinical outcomes in premalignant and early stage head and neck tumors treated on a phase 1 trial of photodynamic therapy. Photodiagnosis Photodyn. Ther.,  2018, 21, 28-35.
[http://dx.doi.org/10.1016/j.pdpdt.2017.10.015] [PMID:  29113960] 
[164] 
Li, J.; Cao, F.; Yin, H.L.; Huang, Z.J.; Lin, Z.T.; Mao, N.; Sun, B.; Wang, G. Ferroptosis: past, present and future. Cell Death Dis.,  2020, 11(2), 88.
[http://dx.doi.org/10.1038/s41419-020-2298-2] [PMID:  32015325] 
[165] 
Zhu, T.; Shi, L.; Yu, C.; Dong, Y.; Qiu, F.; Shen, L.; Qian, Q.; Zhou, G.; Zhu, X. Ferroptosis promotes photodynamic therapy: supramolecular photosensitizer-inducer nanodrug for enhanced cancer treatment. Theranostics,  2019, 9(11), 3293-3307.
[http://dx.doi.org/10.7150/thno.32867] [PMID:  31244955] 
[166] 
Alvarez, M.G.; Prucca, C.; Milanesio, M.E.; Durantini, E.N.; Rivarola, V. Photodynamic activity of a new sensitizer derived from porphyrin-C60 dyad and its biological consequences in a human carcinoma cell line. Int. J. Biochem. Cell Biol.,  2006, 38(12), 2092-2101.
[http://dx.doi.org/10.1016/j.biocel.2006.05.019] [PMID:  16899389] 
[167] 
Shen, L.; Huang, Y.; Chen, D.; Qiu, F.; Ma, C.; Jin, X.; Zhu, X.; Zhou, G.; Zhang, Z. pH-responsive aerobic nanoparticles for effective photodynamic therapy. Theranostics,  2017, 7(18), 4537-4550.
[http://dx.doi.org/10.7150/thno.19546] [PMID:  29158843] 
[168] 
Zhu, T.; Shi, L.; Ma, C.; Xu, L.; Yang, J.; Zhou, G.; Zhu, X.; Shen, L. Fluorinated chitosan-mediated intracellular catalase delivery for enhanced photodynamic therapy of oral cancer. Biomater. Sci.,  2021, 9(3), 658-662.
[http://dx.doi.org/10.1039/D0BM01898H] [PMID:  33463639] 
[169] 
Li, Y.; Sui, H.; Jiang, C.; Li, S.; Han, Y.; Huang, P.; Du, X.; Du, J.; Bai, Y. Dihydroartemisinin increases the sensitivity of photodynamic therapy via NF-κB/HIF-1α/VEGF pathway in esophageal cancer cell in vitro and in vivo. Cell. Physiol. Biochem.,  2018, 48(5), 2035-2045.
[http://dx.doi.org/10.1159/000492541] [PMID:  30099443] 
[170] 
Kim, J.S.; Kim, B.W. Esophageal cancer and head and neck cancer: the earlier, the better. Gut Liver,  2015, 9(2), 131-132.
[http://dx.doi.org/10.5009/gnl15002] [PMID:  25720995] 
[171] 
Watanabe, A.; Hosokawa, M.; Taniguchi, M.; Tsujie, H.; Sasaki, S. Head and neck cancer associated with esophageal cancer. Auris Nasus Larynx,  2007, 34(2), 207-211.
[http://dx.doi.org/10.1016/j.anl.2006.07.012] [PMID:  17070004] 
[172] 
Mallidi, S.; Mai, Z.; Rizvi, I.; Hempstead, J.; Arnason, S.; Celli, J.; Hasan, T. in vivo evaluation of battery-operated light-emitting diode-based photodynamic therapy efficacy using tumor volume and biomarker expression as endpoints. J. Biomed. Opt.,  2015, 20(4), 048003.
[http://dx.doi.org/10.1117/1.JBO.20.4.048003] [PMID:  25909707] 
[173] 
Kareliotis, G.; Liossi, S.; Makropoulou, M. Assessment of singlet oxygen dosimetry concepts in photodynamic therapy through computational modeling. Photodiagnosis Photodyn. Ther.,  2018, 21, 224-233.
[http://dx.doi.org/10.1016/j.pdpdt.2017.12.016] [PMID:  29292205] 
[174] 
Henderson, B.W.; Busch, T.M.; Vaughan, L.A.; Frawley, N.P.; Babich, D.; Sosa, T.A.; Zollo, J.D.; Dee, A.S.; Cooper, M.T.; Bellnier, D.A.; Greco, W.R.; Oseroff, A.R. Photofrin photodynamic therapy can significantly deplete or preserve oxygenation in human basal cell carcinomas during treatment, depending on fluence rate. Cancer Res.,  2000, 60(3), 525-529.
[PMID:  10676629] 
[175] 
Langmack, K.; Mehta, R.; Twyman, P.; Norris, P. Topical photodynamic therapy at low fluence rates--theory and practice. J. Photochem. Photobiol. B,  2001, 60(1), 37-43.
[http://dx.doi.org/10.1016/S1011-1344(01)00116-6] [PMID:  11386679] 
[176] 
Togashi, H.; Uehara, M.; Ikeda, H.; Inokuchi, T. Fractionated photodynamic therapy for a human oral squamous cell carcinoma xenograft. Oral Oncol.,  2006, 42(5), 526-532.
[http://dx.doi.org/10.1016/j.oraloncology.2005.10.006] [PMID:  16466960] 
[177] 
Rhee, Y-H.; Moon, J-H.; Choi, S-H.; Ahn, J-C. Low-level laser therapy promoted aggressive proliferation and angiogenesis through decreasing of transforming growth factor-β1 and increasing of akt/hypoxia inducible factor-1α in anaplastic thyroid cancer. Photomed. Laser Surg.,  2016, 34(6), 229-235.
[http://dx.doi.org/10.1089/pho.2015.3968] [PMID:  27078192] 
[178] 
Piccolo, D.; Kostaki, D. Photodynamic therapy activated by intense pulsed light in the treatment of nonmelanoma skin cancer. Biomedicines,  2018, 6(1), 18.
[http://dx.doi.org/10.3390/biomedicines6010018] [PMID:  29414904] 
[179] 
Micaily, I.; Johnson, J.; Argiris, A. An update on angiogenesis targeting in head and neck squamous cell carcinoma. Cancers Head Neck.,  2020, 5, 1-9.
[180] 
Triesscheijn, M.; Ruevekamp, M.; Aalders, M.; Baas, P.; Stewart, F.A. Outcome of mTHPC mediated photodynamic therapy is primarily determined by the vascular response. Photochem. Photobiol.,  2005, 81(5), 1161-1167.
[http://dx.doi.org/10.1562/2005-04-04-RA-474] [PMID:  15934792] 
[181] 
Kriegs, M.; Clauditz, T.S.; Hoffer, K.; Bartels, J.; Buhs, S.; Gerull, H.; Zech, H.B.; Bußmann, L.; Struve, N.; Rieckmann, T.; Petersen, C.; Betz, C.S.; Rothkamm, K.; Nollau, P.; Münscher, A. Analyzing expression and phosphorylation of the EGF receptor in HNSCC. Sci. Rep.,  2019, 9(1), 13564.
[http://dx.doi.org/10.1038/s41598-019-49885-5] [PMID:  31537844] 
[182] 
Zimmermann, M.; Zouhair, A.; Azria, D.; Ozsahin, M. The epidermal growth factor receptor (EGFR) in head and neck cancer: its role and treatment implications. Radiat. Oncol.,  2006, 1, 11.
[http://dx.doi.org/10.1186/1748-717X-1-11] [PMID:  16722544] 
[183] 
Khaznadar, S.S.; Khan, M.; Schmid, E.; Gebhart, S.; Becker, E-T.; Krahn, T.; von Ahsen, O. EGFR overexpression is not common in patients with head and neck cancer. Cell lines are not representative for the clinical situation in this indication. Oncotarget,  2018, 9(48), 28965-28975.
[http://dx.doi.org/10.18632/oncotarget.25656] [PMID:  29989001] 
[184] 
Chu, P.L.; Shihabuddeen, W.A.; Low, K.P.; Poon, D.J.J.; Ramaswamy, B.; Liang, Z-G.; Nei, W.L.; Chua, K.L.M.; Thong, P.S.P.; Soo, K.C.; Yeo, E.L.L.; Chua, M.L.K. Vandetanib sensitizes head and neck squamous cell carcinoma to photodynamic therapy through modulation of EGFR-dependent DNA repair and the tumour microenvironment. Photodiagnosis Photodyn. Ther.,  2019, 27, 367-374.
[http://dx.doi.org/10.1016/j.pdpdt.2019.06.008] [PMID:  31299389] 
[185] 
Kubin, A.; Wierrani, F.; Burner, U.; Alth, G.; Grünberger, W. Hypericin--the facts about a controversial agent. Curr. Pharm. Des.,  2005, 11(2), 233-253.
[http://dx.doi.org/10.2174/1381612053382287] [PMID:  15638760] 
[186] 
Yee, K.K.L.; Soo, K.C.; Olivo, M. Anti-angiogenic effects of Hypericin-photodynamic therapy in combination with Celebrex in the treatment of human nasopharyngeal carcinoma. Int. J. Mol. Med.,  2005, 16(6), 993-1002.
[http://dx.doi.org/10.3892/ijmm.16.6.993] [PMID:  16273277] 
[187] 
Zhou, Q.; Olivo, M.; Lye, K.Y.K.; Moore, S.; Sharma, A.; Chowbay, B. Enhancing the therapeutic responsiveness of photodynamic therapy with the antiangiogenic agents SU5416 and SU6668 in murine nasopharyngeal carcinoma models. Cancer Chemother. Pharmacol.,  2005, 56(6), 569-577.
[http://dx.doi.org/10.1007/s00280-005-1017-0] [PMID:  16001166] 
[188] 
Sandland, J.; Boyle, R.W. Photosensitizer antibody-drug conjugates: past, present, and future. Bioconjug. Chem.,  2019, 30(4), 975-993.
[http://dx.doi.org/10.1021/acs.bioconjchem.9b00055] [PMID:  30768894] 
[189] 
van Driel, P.B.A.A.; Boonstra, M.C.; Slooter, M.D.; Heukers, R.; Stammes, M.A.; Snoeks, T.J.A.; de Bruijn, H.S.; van Diest, P.J.; Vahrmeijer, A.L.; van Bergen En Henegouwen, P.M.P.; van de Velde, C.J.H.; Löwik, C.W.G.M.; Robinson, D.J.; Oliveira, S. EGFR targeted nanobody-photosensitizer conjugates for photodynamic therapy in a pre-clinical model of head and neck cancer. J. Control. Release,  2016, 229, 93-105.
[http://dx.doi.org/10.1016/j.jconrel.2016.03.014] [PMID:  26988602] 
[190] 
Gillenwater, A. M.; Cognetti, D.; Johnson, J. M.; Curry, J.; Kochuparambil, S. T.; McDonald, D.; Fidler, M. J.; Stenson, K.; Vasan, N.; Razaq, M.; Al,  RM-1929 photoimmunotherapy
in patients with recurrent head and neck
cancer: Results of a multicenter phase 2a open-label clinical
trial. J. Clin. Oncol.,  2018, 36(15_suppl)
[191] 
Chatterjee, D.K.; Fong, L.S.; Zhang, Y. Nanoparticles in photodynamic therapy: an emerging paradigm. Adv. Drug Deliv. Rev.,  2008, 60(15), 1627-1637.
[http://dx.doi.org/10.1016/j.addr.2008.08.003] [PMID:  18930086] 
[192] 
Gusti-Ngurah-Putu, E-P.; Huang, L.; Hsu, Y-C. Effective combined photodynamic therapy with lipid platinum chloride nanoparticles therapies of oral squamous carcinoma tumor inhibition. J. Clin. Med.,  2019, 8(12), E2112.
[http://dx.doi.org/10.3390/jcm8122112] [PMID:  31810241] 
[193] 
Bano, S.; Obaid, G.; Swain, J.W.R.; Yamada, M.; Pogue, B.W.; Wang, K.; Hasan, T. NIR photodynamic destruction of pdac and hnscc nodules using triple-receptor-targeted photoimmuno-nanoconjugates: Targeting heterogeneity in cancer. J. Clin. Med.,  2020, 9(8), E2390.
[http://dx.doi.org/10.3390/jcm9082390] [PMID:  32726945] 
[194] 
He, H.; Nieminen, A-L.; Xu, P. A bioactivatable self-quenched nanogel for targeted photodynamic therapy. Biomater. Sci.,  2019, 7(12), 5143-5149.
[http://dx.doi.org/10.1039/C9BM01237K] [PMID:  31577285] 
[195] 
Xue, X.; Huang, Y.; Bo, R.; Jia, B.; Wu, H.; Yuan, Y.; Wang, Z.; Ma, Z.; Jing, D.; Xu, X.; Yu, W.; Lin, T.Y.; Li, Y. Trojan Horse nanotheranostics with dual transformability and multifunctionality for highly effective cancer treatment. Nat. Commun.,  2018, 9(1), 3653.
[http://dx.doi.org/10.1038/s41467-018-06093-5] [PMID:  30194413] 
Cite As
Current Medicinal Chemistry

Targeting Microenvironment of Melanoma and Head and Neck Cancers in Photodynamic Therapy

Abstract
