Guanidinium-based Integrated Peptide Dendrimers: Pioneer Nanocarrier
in Cancer Therapy

Dilpreet      Singh; Lalu      Muhammad Irham; Amrinder      Singh; Balak Das      Kurmi
Abstract

The landscape of cancer therapy has witnessed a paradigm shift with the emergence of innovative delivery systems, and Guanidinium-based Peptide Dendrimers have emerged as a vanguard in this transformative journey. With their unique molecular architecture and intrinsic biocompatibility, these dendrimers offer a promising avenue for the targeted delivery of therapeutic cargo in cancer treatment. This comprehensive review delves into the intricate world of Guanidinium- based Peptide Dendrimers, unraveling their structural intricacies, mechanisms of action, and advancements that have propelled them from laboratory curiosities to potential clinical champions. Exploiting the potent properties of guanidinium, these dendrimers exhibit unparalleled precision in encapsulating and transporting diverse cargo molecules, ranging from conventional chemotherapeutics to cutting-edge nucleic acids. The review navigates the depths of their design principles, investigating their prowess in traversing the complex terrain of cellular barriers for optimal cargo delivery. Moreover, it delves into emerging trends, such as personalized therapeutic approaches, multimodal imaging, and bioinformatics-driven design, highlighting their potential to redefine the future of cancer therapy. Crucially, the review addresses the pivotal concerns of biocompatibility and safety, examining cytotoxicity profiles, immune responses, and in vivo studies. It underscores the importance of aligning scientific marvels with the stringent demands of clinical applications. Through each section, the narrative underscores the promises and possibilities that Guanidinium-based Peptide Dendrimers hold and how they can potentially reshape the landscape of precision cancer therapy.
Graphical Abstract

[1]
Cheng, Y.; Xu, T. Guanidinium-based peptide dendrimers for drug delivery applications. Adv. Drug Deliv. Rev.,  2017, 110-111, 101-116.

[2]
Misra, S.K.; Moitra, P.; Kondaiah, P.; Bhattacharya, S. Guanidinium-based peptide dendrimers for targeted delivery of therapeutic molecules to cancer cells. J. Control. Release,  2018, 290, 103-121.

[3]
Li, S.; Byrne, J.D.; Kim, J. Self-assembled cationic peptide nanoparticles as an efficient antibacterial agent. Nat. Nanotechnol.,  2011, 6(12), 1-8.

[4]
Jain, K.; Kesharwani, P.; Gupta, U.; Jain, N.K. Dendrimer toxicity: Let’s meet the challenge. Int. J. Pharm.,  2010, 394(1-2), 122-142.
 [http://dx.doi.org/10.1016/j.ijpharm.2010.04.027] [PMID: 20433913]

[5]
Dash, T.K.; Konkimalla, V.B. Poly-є-caprolactone based formulations for drug delivery and tissue engineering: A review. J. Control. Release,  2012, 158(1), 15-33.
 [http://dx.doi.org/10.1016/j.jconrel.2011.09.064] [PMID: 21963774]

[6]
Kannan, R.M.; Nance, E.; Kannan, S.; Tomalia, D.A. Emerging concepts in dendrimer-based nanomedicine: From design principles to clinical applications. J. Intern. Med.,  2014, 276(6), 579-617.
 [http://dx.doi.org/10.1111/joim.12280] [PMID: 24995512]

[7]
Zhang, L.; He, Y.; Yu, D. Polyamidoamine dendrimers-based drug delivery systems for cancer therapy. Eur. J. Med. Chem.,  2019, 161, 164-178.

[8]
Mishiro, K.; Ueno, T.; Wakabayashi, H.; Fukui, M.; Kinuya, S.; Ogawa, K. Synthesis and evaluation of a deltic guanidinium analogue of a cyclic RGD peptide. Org. Biomol. Chem.,  2023, 21(9), 1937-1941.
 [http://dx.doi.org/10.1039/D3OB00089C] [PMID: 36752554]

[9]
Chosy, M.B.; Sun, J.; Rahn, H.P.; Liu, X.; Brčić, J.; Wender, P.A.; Cegelski, L. Vancomycin-polyguanidino dendrimer conjugates inhibit growth of antibiotic-resistant gram-positive and gram-negative bacteria and eradicate biofilm-associated S. aureus. ACS Infect. Dis.,  2024, 10(2), acsinfecdis.3c00168.
 [http://dx.doi.org/10.1021/acsinfecdis.3c00168] [PMID: 38252999]

[10]
Pardeshi, S.; Gholap, A.; More, M.; Togre, N.; Rebello, N.; Giram, P. Dendrimers based antibacterial and antiviral materials. ACS Symp. Ser.,  2023, 1458, 139-169.
 [http://dx.doi.org/10.1021/bk-2023-1458.ch005]

[11]
Liaw, D.J.; Namy, J.L.; Whitefield, B.W. Cationic peptide dendrimers are potent inhibitors of hepatitis B virus (HBV) and hepatitis C virus (HCV) entry. Antiviral Res.,  2012, 93(1), 21-28.
 [PMID: 22841701]

[12]
Galanakou, C.; Dhumal, D.; Peng, L. Amphiphilic dendrimers against antibiotic resistance: Light at the end of the tunnel? Biomater. Sci.,  2023, 11(10), 3379-3393.
 [http://dx.doi.org/10.1039/D2BM01878K] [PMID: 36866708]

[13]
Li, C.; Jia, H.R.; Seidi, F.; Shi, X.; Gu, R.; Guo, Y.; Liu, Y.; Zhu, Y.X.; Wu, F.G.; Xiao, H. Expand and sensitize: Guanidine-functionalized exopolysaccharide nanoparticles cause bacterial cell expansion and antibiotic sensitization. Adv. Funct. Mater.,  2023, 33(51), 2305977.
 [http://dx.doi.org/10.1002/adfm.202305977]

[14]
Huang, S.; Huang, X.; Yan, H. Peptide dendrimers as potentiators of conventional chemotherapy in the treatment of pancreatic cancer in a mouse model. Eur. J. Pharm. Biopharm.,  2022, 170, 121-132.
 [http://dx.doi.org/10.1016/j.ejpb.2021.11.005] [PMID: 34801706]

[15]
Lee, C.C.; MacKay, J.A.; Fréchet, J.M.J.; Szoka, F.C. Designing dendrimers for biological applications. Nat. Biotechnol.,  2005, 23(12), 1517-1526.
 [http://dx.doi.org/10.1038/nbt1171] [PMID: 16333296]

[16]
Kim, S.; Thuy, L.T.; Lee, J.; Choi, J.S. Second-generation polyamidoamine dendrimer conjugated with oligopeptides can enhance plasmid DNA delivery in vitro. Molecules,  2023, 28(22), 7644.
 [http://dx.doi.org/10.3390/molecules28227644] [PMID: 38005366]

[17]
Shaikh, A.Y.; Björkling, F.; Zabicka, D.; Tomczak, M.; Urbas, M.; Domraceva, I.; Kreicberga, A.; Franzyk, H. Structure-activity study of oncocin: On-resin guanidinylation and incorporation of homoarginine, 4-hydroxyproline or 4,4-difluoroproline residues. Bioorg. Chem.,  2023, 141, 106876.
 [http://dx.doi.org/10.1016/j.bioorg.2023.106876] [PMID: 37797458]

[18]
Zhang, Z.; Wang, S.; Cao, Z.; Wen, L.; Zhang, J.; He, B. Novel core-shell structured nanoassemblies based on disulfide-linked dendrimer cores for efficient siRNA delivery. J. Control. Release,  2010, 146(1), 98-109.

[19]
Jiang, L.; Zhou, S.; Zhang, X.; Li, C.; Ji, S.; Mao, H.; Jiang, X. Mitochondrion-specific dendritic lipopeptide liposomes for targeted sub-cellular delivery. Nat. Commun.,  2021, 12(1), 2390.
 [http://dx.doi.org/10.1038/s41467-021-22594-2] [PMID: 33888699]

[20]
Guan, Q.; Wang, G.B.; Zhou, L.L.; Li, W.Y.; Dong, Y.B. Nanoscale covalent organic frameworks as theranostic platforms for oncotherapy: Synthesis, functionalization, and applications. Nanoscale Adv.,  2020, 2(9), 3656-3733.
 [http://dx.doi.org/10.1039/D0NA00537A] [PMID: 36132748]

[21]
Zhu, M.; Wang, X.; Xie, R.; Wang, Y.; Xu, X.; Burger, J.; Gong, S. Guanidinium-rich lipopeptide-based nanoparticle enables efficient gene editing in skeletal muscles. ACS Appl. Mater. Interfaces,  2023, 15(8), 10464-10476.
 [http://dx.doi.org/10.1021/acsami.2c21683] [PMID: 36800641]

[22]
Aldemir, N.; Vallet, C.; Knauer, S.K.; Schmuck, C.; Hirschhäuser, C. A fluorophore-labeled lysine dendrimer with an oxo-anion-binding motif for tracking gene transfection. ChemBioChem,  2023, 24(15), e202300296.
 [http://dx.doi.org/10.1002/cbic.202300296] [PMID: 37071493]

[23]
Sánchez-Milla, M.; Muñoz-Moreno, L.; Sánchez-Nieves, J.; Malý, M.; Gómez, R.; Carmena, M.J.; de la Mata, F.J. Anticancer activity of dendriplexes against advanced prostate cancer from protumoral peptides and cationic carbosilane dendrimers. Biomacromolecules,  2019, 20(3), 1224-1234.
 [http://dx.doi.org/10.1021/acs.biomac.8b01632] [PMID: 30669830]

[24]
Mogaki, R.; Hashim, P.K.; Okuro, K.; Aida, T. Guanidinium-based “molecular glues” for modulation of biomolecular functions. Chem. Soc. Rev.,  2017, 46(21), 6480-6491.
 [http://dx.doi.org/10.1039/C7CS00647K] [PMID: 29034942]

[25]
Wiwattanapatapee, R.; Carreño-Gómez, B.; Malik, N.; Duncan, R. Anionic PAMAM dendrimers rapidly cross adult rat intestine in vitro: A potential oral delivery system? Pharm. Res.,  2000, 17(8), 991-998.
 [http://dx.doi.org/10.1023/A:1007587523543] [PMID: 11028947]

[26]
Ramasamy, T.; Ruttala, H.B.; Gupta, B.; Poudel, B.K.; Choi, H.G.; Yong, C.S.; Kim, J.O.; Yong, C.S.; Kim, J.O. Smart chemistry-based nanosized drug delivery systems for systemic applications: A comprehensive review. J. Control. Release,  2017, 258, 226-253.
 [http://dx.doi.org/10.1016/j.jconrel.2017.04.043] [PMID: 28472638]

[27]
Zhao, B.; Zhang, X.; Bickle, M.S.; Fu, S.; Li, Q.; Zhang, F. Development of polypeptide-based materials toward messenger RNA delivery. Nanoscale,  2024, 16(5), 2250-2264.
 [http://dx.doi.org/10.1039/D3NR05635J] [PMID: 38213302]

[28]
He, X.; Xiong, S.; Sun, Y.; Zhong, M.; Xiao, N.; Zhou, Z.; Wang, T.; Tang, Y.; Xie, J. Recent progress of rational modified nanocarriers for cytosolic protein delivery. Pharmaceutics,  2023, 15(6), 1610.
 [http://dx.doi.org/10.3390/pharmaceutics15061610] [PMID: 37376059]

[29]
Zhang, Z.; Gao, X.; Li, Y.; Lv, J.; Wang, H.; Cheng, Y. Catechol-based polymers with high efficacy in cytosolic protein delivery. CCS Chemistry,  2023, 5(6), 1411-1421.
 [http://dx.doi.org/10.31635/ccschem.022.202202098]

[30]
Luther, D.C.; Goswami, R.; Lee, Y.W.; Jeon, T.; Huang, R.; Elia, J.L.; Nagaraj, H.; Bijlsma, J.J.E.; Piest, M.; Langereis, M.A.; Rotello, V.M. Non-viral vaccination through cationic guanidium polymer-pDNA polyplex mediated gene transfer. Nanoscale,  2023, 15(24), 10351-10359.
 [http://dx.doi.org/10.1039/D2NR06428F] [PMID: 37288531]

[31]
Opanasopit, P.; Ngawhirunpat, T.; Rojanarata, T.; Apirakaramwong, A.; Panomsuk, S.; Ruktanonchai, U. Chitosan conjugated PAMAM dendrimers for the delivery of antisense oligonucleotides targeting anti-apoptotic Bcl-2 mRNA in leukemia cells. Eur. J. Pharm. Biopharm.,  2010, 74(3), 474-483.
 [PMID: 20060469]

[32]
He, Y.; Huang, W.; Zheng, Q.; Huang, H.; Ouyang, D.; Zhang, S.; Yan, X.; Ji, Y.; Wu, Y.; Lin, Z. Two-dimensional guani-dinium-based covalent organic nanosheets for controllable recognition and specific enrichment of global/multi-phosphopeptides. Talanta,  2021, 233, 122497.
 [http://dx.doi.org/10.1016/j.talanta.2021.122497] [PMID: 34215115]

[33]
Liu, X.; Wen, Y.; Li, X.; Chen, Y.; Wang, Q.; Wang, Y. Biodegradable cationic PEG-PEI-PBLG hyperbranched block copolymers for efficient and safe gene delivery. Polym. Chem.,  2013, 4(14), 4026-4036.

[34]
Ma, Y.; Mou, Q.; Zhang, Y. Versatile cationic lipids for siRNA delivery. J. Control. Release,  2010, 143(3), 290-300.
 [PMID: 20074598]

[35]
Wang, K.; Zhang, T.; Liu, L. Probing the stability of poly(amido amine) dendrimer-plasmid DNA complexes: Impact on in vitro and in vivo gene delivery. J. Pharm. Sci.,  2015, 104(6), 2063-2073.

[36]
Choi, Y.; Lee, J.E.; Lee, J.H. A biocompatible tumoral pH-responsive polymersome for efficient siRNA delivery. J. Control. Release,  2016, 239, 94-106.

[37]
Cheng, Y. Design of polymers for intracellular protein and peptide delivery. Chin. J. Chem.,  2021, 39(6), 1443-1449.
 [http://dx.doi.org/10.1002/cjoc.202000655]

[38]
Yin, K.; Zhang, Z.; Li, X.; Yang, L.; Tachibana, K.; Hirano, S. Polymer electrolytes based on dicationic polymeric ionic liquids: Application in lithium metal batteries. J. Mater. Chem. A Mater. Energy Sustain.,  2015, 3(1), 170-178.
 [http://dx.doi.org/10.1039/C4TA05106H]

[39]
Li, M.; Yang, L.; Fang, S.; Dong, S. Novel polymeric ionic liquid membranes as solid polymer electrolytes with high ionic conductivity at moderate temperature. J. Membr. Sci.,  2011, 366(1-2), 245-250.
 [http://dx.doi.org/10.1016/j.memsci.2010.10.004]

[40]
Adami, R.C.; Seth, S.; Harvie, P.; Johns, R.; Fam, R.; Fosnaugh, K.; Zhu, T.; Farber, K.; McCutcheon, M.; Goodman, T.T.; Liu, Y.; Chen, Y.; Kwang, E.; Templin, M.V.; Severson, G.; Brown, T.; Vaish, N.; Chen, F.; Charmley, P.; Polisky, B.; Houston, M.E., Jr. An amino acid-based amphoteric liposomal delivery system for systemic administration of siRNA. Mol. Ther.,  2011, 19(6), 1141-1151.
 [http://dx.doi.org/10.1038/mt.2011.56] [PMID: 21505423]

[41]
Alfei, S. Cationic materials for gene therapy: A look back to the birth and development of 2,2-bis-(hydroxymethyl)propanoic acid-based dendrimer scaffolds. Int. J. Mol. Sci.,  2023, 24(21), 16006.
 [http://dx.doi.org/10.3390/ijms242116006] [PMID: 37958989]

[42]
Padnya, P.; Mostovaya, O.; Ovchinnikov, D.; Shiabiev, I.; Pysin, D.; Akhmedov, A.; Mukhametzyanov, T.; Lyubina, A.; Voloshina, A.; Petrov, K.; Stoikov, I. Combined antimicrobial agents based on self-assembled PAMAM-calix-dendrimers/lysozyme nanoparticles: Design, antibacterial properties and cytotoxicity. J. Mol. Liq.,  2023, 389, 122838.
 [http://dx.doi.org/10.1016/j.molliq.2023.122838]

[43]
Wong, K.H.; Guo, Z.; Law, M.K.; Chen, M. Functionalized PAMAM constructed nanosystems for biomacromolecule delivery. Biomater. Sci.,  2023, 11(5), 1589-1606.
 [http://dx.doi.org/10.1039/D2BM01677J] [PMID: 36692071]

[44]
Ray, R.; Ghosh, S.; Panja, P.; Jana, N.R. Rapid mitochondria targeting by arginine-terminated, sub-10 nm nanoprobe via direct cell membrane penetration. ACS Appl. Bio Mater.,  2023, 6(6), 2338-2344.
 [http://dx.doi.org/10.1021/acsabm.3c00187] [PMID: 37196150]

[45]
Lisi, D.; Vezzoni, C.A.; Casnati, A.; Sansone, F.; Salvio, R. Intra- and intermolecular cooperativity in the catalytic activity of phosphodiester cleavage by self-assembled systems based on guanidinylated Calix[4]arenes. Chemistry,  2023, 29(12), e202203213.
 [http://dx.doi.org/10.1002/chem.202203213] [PMID: 36382737]

[46]
Wang, C.; He, W.; Wang, F.; Yong, H.; Bo, T.; Yao, D.; Zhao, Y.; Pan, C.; Cao, Q.; Zhang, S.; Li, M. Recent progress of non-linear topological structure polymers: Synthesis, and gene delivery. J. Nanobiotechnology,  2024, 22(1), 1-20.
 [http://dx.doi.org/10.1186/s12951-023-02253-y] [PMID: 38167129]

[47]
Beer, P.D.; Gale, P.A. Anion recognition and sensing: the state of the art and future perspectives. Angew. Chem. Int. Ed.,  2001, 40(3), 486-516.
 [http://dx.doi.org/10.1002/1521-3773(20010202)40:3<486::AID-ANIE486>3.0.CO;2-P] [PMID: 11180358]

[48]
Qiao, L.Z.; Yu, C.M.; Sun, R.T. Preparation of amino-functionalized guanidinium ionic liquid-modified magnetic materials and application in solid-phase extraction of pollutants in water. J. Anal. Test.,  2022, 6(4), 401-410.
 [http://dx.doi.org/10.1007/s41664-021-00188-7]

[49]
Tang, H.; Xu, X.; Chen, Y.; Xin, H.; Wan, T.; Li, B.; Pan, H.; Li, D.; Ping, Y. Reprogramming the tumor microenvironment through second-near-infrared-window photothermal genome editing of PD-L1 mediated by supramolecular gold nanorods for enhanced cancer immunotherapy. Adv. Mater.,  2021, 33(12), 2006003.
 [http://dx.doi.org/10.1002/adma.202006003] [PMID: 33538047]

[50]
Wexselblatt, E.; Esko, J.D.; Tor, Y. On guanidinium and cellular uptake. J. Org. Chem.,  2014, 79(15), 6766-6774.
 [http://dx.doi.org/10.1021/jo501101s] [PMID: 25019333]

[51]
Romani, C.; Gagni, P.; Sponchioni, M.; Volonterio, A. Selectively fluorinated PAMAM–arginine conjugates as gene delivery vectors. Bioconjug. Chem.,  2023, 34(6), 1084-1095.
 [http://dx.doi.org/10.1021/acs.bioconjchem.3c00139] [PMID: 37221455]

[52]
Gao, Y.; Liu, X.; Chen, N.; Yang, X.; Tang, F. Recent advance of liposome nanoparticles for nucleic acid therapy. Pharmaceutics,  2023, 15(1), 178.
 [http://dx.doi.org/10.3390/pharmaceutics15010178] [PMID: 36678807]

[53]
Shi, Z.; Yang, Y.; Guo, Z.; Feng, S.; Wan, Y. A cathepsin B/GSH dual-responsive fluorinated peptide for effective siRNA delivery to cancer cells. Bioorg. Chem.,  2023, 135, 106485.
 [http://dx.doi.org/10.1016/j.bioorg.2023.106485] [PMID: 36963370]

[54]
Hentzen, N.B.; Mogaki, R.; Otake, S.; Okuro, K.; Aida, T. Intracellular photoactivation of Caspase-3 by molecular glues for spatiotemporal apoptosis induction. J. Am. Chem. Soc.,  2020, 142(18), 8080-8084.
 [http://dx.doi.org/10.1021/jacs.0c01823] [PMID: 32275408]

[55]
Greco, F.; Vicent, M.J. Combination therapy: Opportunities and challenges for polymer–drug conjugates as anticancer nanomedicines. Adv. Drug Deliv. Rev.,  2009, 61(13), 1203-1213.
 [http://dx.doi.org/10.1016/j.addr.2009.05.006] [PMID: 19699247]

[56]
Girase, M.L.; Patil, P.G.; Ige, P.P. Polymer-drug conjugates as nanomedicine: A review. Int. J. Polym. Mater.,  2020, 69(15), 990-1014.
 [http://dx.doi.org/10.1080/00914037.2019.1655745]

[57]
Jain, V.; Jain, S.; Mahajan, S.C. Nanomedicines based drug delivery systems for anti-cancer targeting and treatment. Curr. Drug Deliv.,  2015, 12(2), 177-191.
 [http://dx.doi.org/10.2174/1567201811666140822112516] [PMID: 25146439]

[58]
Feng, Q.; Tong, R. Anticancer nanoparticulate polymer-drug conjugate. Bioeng. Transl. Med.,  2016, 1(3), 277-296.
 [http://dx.doi.org/10.1002/btm2.10033] [PMID: 29313017]

[59]
Nair, C.R.; Sreejalekshmi, K.G. PAMAM–guanylthiourea conjugates mask furin’s substrate binding site: Mechanistic insights from molecular docking and molecular dynamics studies assist the design of potential furin inhibitors. New J. Chem.,  2023, 47(26), 12468-12476.
 [http://dx.doi.org/10.1039/D3NJ00703K]

[60]
Wang, X.; Li, Y.; Wang, X.; Sandoval, D.M.; He, Z.; A, S.; Sáez, I.L.; Wang, W. Guanidyl-rich poly(β Amino Ester)s for universal functional cytosolic protein delivery and clustered regularly interspaced short palindromic repeats (CRISPR) Cas9 ribonucleoprotein based gene editing. ACS Nano,  2023, 17(18), 17799-17810.
 [http://dx.doi.org/10.1021/acsnano.3c03269] [PMID: 37669145]

[61]
Son, H.; Shin, J.; Park, J. Recent progress in nanomedicine-mediated cytosolic delivery. RSC Advances,  2023, 13(15), 9788-9799.
 [http://dx.doi.org/10.1039/D2RA07111H] [PMID: 36998521]

[62]
Eskandari, S.; Rezayof, A.; Asghari, S.M.; Hashemizadeh, S. Neurobiochemical characteristics of arginine-rich peptides explain their potential therapeutic efficacy in neurodegenerative diseases. Neuropeptides,  2023, 101, 102356.
 [http://dx.doi.org/10.1016/j.npep.2023.102356] [PMID: 37390744]

[63]
Chen, C.; Gao, P.; Wang, H.; Cheng, Y.; Lv, J. Histidine-based coordinative polymers for efficient intracellular protein delivery via enhanced protein binding, cellular uptake, and endosomal escape. Biomater. Sci.,  2023, 11(5), 1765-1775.
 [http://dx.doi.org/10.1039/D2BM01541B] [PMID: 36648450]

[64]
Cai, X.; Zhu, H.; Zhang, Y.; Gu, Z. Highly efficient and safe delivery of VEGF siRNA by bioreducible fluorinated peptide dendrimers for cancer therapy. ACS Appl. Mater. Interfaces,  2017, 9(11), 9402-9415.
 [http://dx.doi.org/10.1021/acsami.6b16689] [PMID: 28228013]

[65]
Cheng, Y.; Zhao, L.; Li, Y.; Xu, T. Design of biocompatible dendrimers for cancer diagnosis and therapy: Current status and future perspectives. Chem. Soc. Rev.,  2011, 40(5), 2673-2703.
 [http://dx.doi.org/10.1039/c0cs00097c] [PMID: 21286593]

[66]
Gorzkiewicz, M.; Konopka, M.; Janaszewska, A.; Tarasenko, I.I.; Sheveleva, N.N.; Gajek, A.; Neelov, I.M.; Klajnert-Maculewicz, B. Application of new lysine-based peptide dendrimers D3K2 and D3G2 for gene delivery: Specific cytotoxicity to cancer cells and transfection in vitro. Bioorg. Chem.,  2020, 95, 103504.
 [http://dx.doi.org/10.1016/j.bioorg.2019.103504] [PMID: 31864904]

[67]
Zhang, C.; Pan, D.; Luo, K.; She, W.; Guo, C.; Yang, Y.; Gu, Z. Peptide dendrimer-Doxorubicin conjugate-based nanoparticles as an enzyme-responsive drug delivery system for cancer therapy. Adv. Healthc. Mater.,  2014, 3(8), 1299-1308.
 [http://dx.doi.org/10.1002/adhm.201300601] [PMID: 24706635]

[68]
Liu, J.; Liu, J.; Chu, L.; Wang, Y.; Duan, Y.; Feng, L.; Yang, C.; Wang, L.; Kong, D. Novel peptide-dendrimer conjugates as drug carriers for targeting nonsmall cell lung cancer. Int. J. Nanomedicine,  2010, 6, 59-69.
 [PMID: 21289982]

[69]
Dong, Y.; Chen, Y.; Zhu, D.; Shi, K.; Ma, C.; Zhang, W.; Rocchi, P.; Jiang, L.; Liu, X. Self-assembly of amphiphilic phospholipid peptide dendrimer-based nanovectors for effective delivery of siRNA therapeutics in prostate cancer therapy. J. Control. Release,  2020, 322, 416-425.
 [http://dx.doi.org/10.1016/j.jconrel.2020.04.003] [PMID: 32247806]

[70]
Cooper, B.M.; Iegre, J.; O’ Donovan, D.H.; Ölwegård Halvarsson, M.; Spring, D.R. Peptides as a platform for targeted therapeutics for cancer: Peptide–drug conjugates (PDCs). Chem. Soc. Rev.,  2021, 50(3), 1480-1494.
 [http://dx.doi.org/10.1039/D0CS00556H] [PMID: 33346298]

[71]
Saluja, V.; Mishra, Y.; Mishra, V.; Giri, N.; Nayak, P. Dendrimers based cancer nanotheranostics: An overview. Int. J. Pharm.,  2021, 600, 120485.
 [http://dx.doi.org/10.1016/j.ijpharm.2021.120485] [PMID: 33744447]

[72]
Xie, R.; Wang, Y.; Burger, J.C.; Li, D.; Zhu, M.; Gong, S. Non-viral approaches for gene therapy and therapeutic genome editing across the blood–brain barrier. Med-X,  2023, 1(1), 6.
 [http://dx.doi.org/10.1007/s44258-023-00004-0] [PMID: 37485250]

[73]
Kalantari, F.; Rezayati, S.; Ramazani, A.; Poor Heravi, M. Syntheses and structures of magnetic nanodendrimers and their catalytic application in organic synthesis. Appl. Organomet. Chem.,  2023, 37(6), e7064.
 [http://dx.doi.org/10.1002/aoc.7064]

[74]
Zhou, L.; Gao, G.; Ma, Z.; Zhang, Z.; Gu, Z.; Yu, L.; Li, X.; Zhang, N.; Qian, L.; Tao, Z.; Sun, T. Gold nanoclusters enhance the efficacy of the polymer-based chaperone in restoring and maintaining the native conformation of human islet amyloid polypeptide. ACS Appl. Mater. Interfaces,  2023, 15(2), 3409-3419.
 [http://dx.doi.org/10.1021/acsami.2c17777] [PMID: 36598876]

[75]
Zhu, D.; Zhang, H.; Huang, Y.; Lian, B.; Ma, C.; Han, L.; Chen, Y.; Wu, S.; Li, N.; Zhang, W.; Liu, X. A self-assembling amphiphilic peptide dendrimer-based drug delivery system for cancer therapy. Pharmaceutics,  2021, 13(7), 1092.
 [http://dx.doi.org/10.3390/pharmaceutics13071092] [PMID: 34371783]

[76]
Liu, L.; Kuang, Y.; Yang, H.; Chen, Y. An amplification strategy using DNA-Peptide dendrimer probe and mass spectrometry for sensitive MicroRNA detection in breast cancer. Anal. Chim. Acta,  2019, 1069, 73-81.
 [http://dx.doi.org/10.1016/j.aca.2019.04.009] [PMID: 31084743]

[77]
Xie, F.; Li, R.; Shu, W.; Zhao, L.; Wan, J. Self-assembly of Peptide dendrimers and their bio-applications in theranostics. Mater. Today Bio,  2022, 14, 100239.
 [http://dx.doi.org/10.1016/j.mtbio.2022.100239] [PMID: 35295319]

[78]
Zhang, C.; Pan, D.; Luo, K.; Li, N.; Guo, C.; Zheng, X.; Gu, Z. Dendrimer–doxorubicin conjugate as enzyme-sensitive and polymeric nanoscale drug delivery vehicle for ovarian cancer therapy. Polym. Chem.,  2014, 5(18), 5227-5235.
 [http://dx.doi.org/10.1039/C4PY00601A]

[79]
Subhan, M.A.; Torchilin, V.P. Biopolymer-based nanosystems for siRNA drug delivery to solid tumors including breast cancer. Pharmaceutics,  2023, 15(1), 153.
 [http://dx.doi.org/10.3390/pharmaceutics15010153] [PMID: 36678782]

[80]
Yang, J.; Luo, G.F. Peptide-based vectors for gene delivery. Chemistry,  2023, 5(3), 1696-1718.
 [http://dx.doi.org/10.3390/chemistry5030116]

[81]
Gasparello, J.; Papi, C.; Zurlo, M.; Volpi, S.; Gambari, R.; Corradini, R.; Casnati, A.; Sansone, F.; Finotti, A. Cationic Calix[4]arene vectors to efficiently deliver AntimiRNA peptide nucleic acids (PNAs) and miRNA mimics. Pharmaceutics,  2023, 15(8), 2121.
 [http://dx.doi.org/10.3390/pharmaceutics15082121] [PMID: 37631335]

[82]
Fang, X.; Gao, K.; Huang, J.; Liu, K.; Chen, L.; Piao, Y.; Liu, X.; Tang, J.; Shen, Y.; Zhou, Z. Molecular level precision and high molecular weight peptide dendrimers for drug-specific delivery. J. Mater. Chem. B Mater. Biol. Med.,  2021, 9(41), 8594-8603.
 [http://dx.doi.org/10.1039/D1TB01157J] [PMID: 34705008]

[83]
Mukherjee, S.; Mukherjee, S.; Abourehab, M.A.S.; Sahebkar, A.; Kesharwani, P. Exploring dendrimer-based drug delivery systems and their potential applications in cancer immunotherapy. Eur. Polym. J.,  2022, 177, 111471.
 [http://dx.doi.org/10.1016/j.eurpolymj.2022.111471]

[84]
Yang, H. Targeted nanosystems: Advances in targeted dendrimers for cancer therapy. Nanomedicine,  2016, 12(2), 309-316.
 [http://dx.doi.org/10.1016/j.nano.2015.11.012] [PMID: 26706410]

[85]
Tarach, P.; Janaszewska, A. Recent advances in preclinical research using PAMAM dendrimers for cancer gene therapy. Int. J. Mol. Sci.,  2021, 22(6), 2912.
 [http://dx.doi.org/10.3390/ijms22062912] [PMID: 33805602]

[86]
Modi, D.A.; Sunoqrot, S.; Bugno, J.; Lantvit, D.D.; Hong, S.; Burdette, J.E. Targeting of follicle stimulating hormone peptide-conjugated dendrimers to ovarian cancer cells. Nanoscale,  2014, 6(5), 2812-2820.
 [http://dx.doi.org/10.1039/C3NR05042D] [PMID: 24468839]

[87]
He, X.; Alves, C.S.; Oliveira, N.; Rodrigues, J.; Zhu, J.; Bányai, I.; Tomás, H.; Shi, X. RGD peptide-modified multifunctional dendrimer platform for drug encapsulation and targeted inhibition of cancer cells. Colloids Surf. B Biointerfaces,  2015, 125, 82-89.
 [http://dx.doi.org/10.1016/j.colsurfb.2014.11.004] [PMID: 25437067]

[88]
Guo, R.; Shi, X. Dendrimers in cancer therapeutics and diagnosis. Curr. Drug Metab.,  2012, 13(8), 1097-1109.
 [http://dx.doi.org/10.2174/138920012802850010] [PMID: 22380011]

[89]
Kolimi, P.; Narala, S.; Youssef, A.A.A.; Nyavanandi, D.; Dudhipala, N. A systemic review on development of mesoporous nanoparticles as a vehicle for transdermal drug delivery. Nanotheranostics,  2023, 7(1), 70-89.
 [http://dx.doi.org/10.7150/ntno.77395] [PMID: 36593800]

[90]
Stefanovic, S. Development of functional star-shaped polypeptides for biomedical applications,  2023.

[91]
Nigam, S.; Bahadur, D. Dendrimer-conjugated iron oxide nanoparticles as stimuli-responsive drug carriers for thermally-activated chemotherapy of cancer. Colloids Surf. B Biointerfaces,  2017, 155, 182-192.
 [http://dx.doi.org/10.1016/j.colsurfb.2017.04.025] [PMID: 28431327]

[92]
Carvalho, M.R.; Carvalho, C.R.; Maia, F.R.; Caballero, D.; Kundu, S.C.; Reis, R.L.; Oliveira, J.M. Peptide-modified dendrimer nanoparticles for targeted therapy of colorectal cancer. Adv. Ther.,  2019, 2(11), 1900132.
 [http://dx.doi.org/10.1002/adtp.201900132]

[93]
Arora, V.; Abourehab, M.A.S.; Modi, G.; Kesharwani, P. Dendrimers as prospective nanocarrier for targeted delivery against lung cancer. Eur. Polym. J.,  2022, 180, 111635.
 [http://dx.doi.org/10.1016/j.eurpolymj.2022.111635]

[94]
Sheikh, A.; Md, S.; Kesharwani, P. RGD engineered dendrimer nanotherapeutic as an emerging targeted approach in cancer therapy. J. Control. Release,  2021, 340, 221-242.
 [http://dx.doi.org/10.1016/j.jconrel.2021.10.028] [PMID: 34757195]

[95]
Sapra, R.; Verma, R.P.; Maurya, G.P.; Dhawan, S.; Babu, J.; Haridas, V. Designer peptide and protein dendrimers: A cross-sectional analysis. Chem. Rev.,  2019, 119(21), 11391-11441.
 [http://dx.doi.org/10.1021/acs.chemrev.9b00153] [PMID: 31556597]

[96]
Liu, F.H.; Hou, C.Y.; Zhang, D.; Zhao, W.J.; Cong, Y.; Duan, Z.Y.; Qiao, Z.Y.; Wang, H. Enzyme-sensitive cytotoxic peptide–dendrimer conjugates enhance cell apoptosis and deep tumor penetration. Biomater. Sci.,  2018, 6(3), 604-613.
 [http://dx.doi.org/10.1039/C7BM01182B] [PMID: 29406549]

[97]
Li, N.; Li, N.; Yi, Q.; Luo, K.; Guo, C.; Pan, D.; Gu, Z. Amphiphilic peptide dendritic copolymer-doxorubicin nanoscale conjugate self-assembled to enzyme-responsive anti-cancer agent. Biomaterials,  2014, 35(35), 9529-9545.
 [http://dx.doi.org/10.1016/j.biomaterials.2014.07.059] [PMID: 25145854]

[98]
Li, N.; Duan, Z.; Wang, L.; Guo, C.; Zhang, H.; Gu, Z.; Gong, Q.; Luo, K. An amphiphilic PEGylated peptide dendron-gemcitabine prodrug-based nanoagent for cancer therapy. Macromol. Rapid Commun.,  2021, 42(12), 2100111.
 [http://dx.doi.org/10.1002/marc.202100111] [PMID: 33871122]

[99]
Somani, S.; Dufès, C. Applications of dendrimers for brain delivery and cancer therapy. Nanomedicine,  2014, 9(15), 2403-2414.
 [http://dx.doi.org/10.2217/nnm.14.130] [PMID: 25413857]

[100]
Yang, J.; Zhang, Q.; Chang, H.; Cheng, Y. Surface-engineered dendrimers in gene delivery. Chem. Rev.,  2015, 115(11), 5274-5300.
 [http://dx.doi.org/10.1021/cr500542t] [PMID: 25944558]

[101]
Chyi, LC; Le Yi, C; Kumar, PV. Dendrimer-based nanocomposites for the production of RNA delivery systems. OpenNano,  2023, 100173.

[102]
Cruz, A.; Barbosa, J.; Antunes, P.; Bonifácio, V.D.B.; Pinto, S.N. A glimpse into dendrimers integration in cancer imaging and theranostics. Int. J. Mol. Sci.,  2023, 24(6), 5430.
 [http://dx.doi.org/10.3390/ijms24065430] [PMID: 36982503]

[103]
Dannert, C.; Mardal, I.; Lale, R.; Stokke, B.T.; Dias, R.S. DNA condensation by peptide-conjugated PAMAM dendrimers. Influence of peptide charge. ACS Omega,  2023, 8(47), 44624-44636.
 [http://dx.doi.org/10.1021/acsomega.3c05140] [PMID: 38046290]
Cite As
Protein & Peptide Letters

Guanidinium-based Integrated Peptide Dendrimers: Pioneer Nanocarrier in Cancer Therapy

Abstract

Graphical Abstract
