Brain Tumor Targeting Drug Delivery Systems: Advanced Nanoscience for Theranostics Applications

The brain is an efficient processor of information. It is the most complex and sensitive organ in the body and is responsible for all functions of the body, including serving as the coordinating center for all sensations, mobility, emotions, and intellect. The magnitude of its myriad function is often realized usually when there is a disruption of the nervous system due to injury, disease, or inherited predispositions. Neuroscience is the field of study that endeavors to make sense of such diverse questions; at the same time, it points the way toward the effective treatment of dysfunctions. The two-way channel of information: findings from the laboratory leading towards stricter criteria for diagnosing brain disorders and more effective methods for treating them and in turn, the clinician's increasingly acute skills of diagnosis and observation that supply the research scientist with more precise data for study in the lab diligently expands the field of neuroscience. Tumors of the brain produce neurological manifestations through several mechanisms. Stronger hypotheses about the mechanism of a disease can point the way toward more effective treatments and new possibilities for a cure. In highly complex disorders of the brain, in which many factors genetic, environmental, epidemiological, even social and psychological—play a part, broadly based hypotheses are exceedingly useful. With the advancements in technology and a better understanding of brain anatomy and physiology, the quest to discover an efficient cure for life-threatening tumors of the brain is underway.

Brain tumor is considered to be the most detrimental disease found in humans. Amongst the various brain tumors, glioblastoma has emerged as a highly invasive malignant disease that has contributed to significant mortality worldwide. Despite surgical and drug innovations, most of the patients suffering from brain tumours have shown poor prognosis, with a median life span. The presence of the blood-brain barrier (BBB) acts as a protective layer outside the brain for most of the conventional, diagnostic and therapeutic agents, which in turn leads to poor diagnosis and less efficacy in most clinical subjects. In recent years, multifunctional nanotechnology systems have been employed to deliver theranostic agents to the brain, showing promising outcomes in the treatment of various forms of cancer. The present chapter provides comprehensive information on the most recent developments in BBB-crossing nanotechnology, with a slight focus on the thoughtful design of multifunctional nanoplatforms for effective BBB penetration, accurate tumor imaging, and substantial brain tumor inhibition. Besides, various physiological barriers and transportation mechanisms, different drug delivery systems for brain tumors are also highlighted. Furthermore, major advancements in brain tumor theranostics pertaining to employing different nanosystems such as liposomes, polymeric nanoparticles, bio-nano particles, and inorganic-nanoparticles for effective nano-drug delivery for theranostics in brain tumors have also been discussed. 

Theranostics, a dual strategy, helps in better tumor imaging, the biodistribution of drugs (the ability to direct therapeutic agents to the tumor site), and understanding the progress and effectiveness of therapy. Theranostics is an emerging technology for the diagnosis and management of brain tumors which differ from peripheral tumors in several ways because of their complexity in the genesis of oncogenes. Several factors must be considered for successful brain tumor-targeted drug delivery. Nanotheranostics for brain cancer therapies have been identified now, and polymeric nanoparticles (PNP) are one of the most efficient and promising nanotechnological platforms. They can be utilized as a new imaging method to optimize chemotherapeutic drug delivery into brain tumors while reducing the drug's dissemination and toxicity in healthy people. Smart carriers and theranostic nanoparticles can diagnose, deliver, and track the therapeutic response synchronized. This chapter gives an insight into superparamagnetic, ultrasound-triggered radionuclide bearing, and fluorescent PNPs as potential theranostic approaches for brain tumor management. 

The treatment of brain tumours is often a challenging task due to the low permeability of drugs through the blood-brain barrier and their poor penetration into the tumour tissues. Liposomes enhance the delivery of chemotherapeutics to the brain without using any invasive approach. Liposomes are biomimetic nanocarriers that exhibit good biocompatibility, high loading capacity, and the ability to reduce the amount of encapsulated drugs. It is a promising candidate performing a dual function of both drug delivery and diagnosis. This approach helps to locate the tumour tissue with appropriate biodistribution of liposomes. The theranostic liposomes provide a platform for imaging tumour cells for early diagnosis and simultaneously, delivery to the brain enhances the targeting delivery. Fluorescent dyes, magnetic resonance imaging, and nuclear imaging are the few approaches used in the diagnosis of tumour cells. A new approach involving semi-conductor-based quantum dots has emerged as an imaging reagent for brain tissues. The theranostic application of liposomes provides the real-time monitoring of the administered drug, reducing the risk of under-or overdosing and allowing for more customized therapy regimens. This chapter highlights the techniques for directing liposomes to solid tumours in-depth, potential targets in cancer cells, such as extracellular and intracellular targets, and targets in the tumour microenvironment or vasculature. Additionally, this chapter also concludes recent efforts for improving anticancer drug delivery at the tumour site using surface functionalization techniques, and the different contrast agents which help in diagnosis are discussed.

Brain tumors have become one of the deadliest types of cancer. Tragically, the blood-brain barrier (BBB), an astringent regulatory, well-coordinated, and effectual obstacle, prevents most substances from passing through it. As a result, breaking through this hurdle is amongst the most difficult challenges in devising effective CNS therapies. In the USA, approximately seven lakh people have a principal brain malignancy, with an ample eighty-five thousand predicted to be afflicted by 2021. Capillaries are essential for delivering oxygen and nutrients to all body tissue and vital organs. The capillaries that vascularize the CNS have a special feature known as the blood-brain barrier, which enables such vessels to firmly enforce the transfer of ions, substances, and cells in-between the blood-brain barrier. This accurate estimation of CNS homeostasis leads to proper neuronal function while also protecting neural tissue from toxic substances and microorganisms, and changes in such mechanical strength are a major aspect of the pathology and transformation of various neurological diseases. Theranostic strategies were also postulated and deemed enticing in recent times. Due to the smaller size, better topical functionalization, and capability to integrate various processing elements in one system, nanotechnology is beneficial for this system. For cancer therapy, the structure of nanotherapeutic systems focusing on diagnostic and therapeutic applications is increasing tremendously. This dual system is extremely useful for personalized medicine-based clinical applications because it seeks to analyze the position of malignancy, the biodistribution of nanosized systems, along with an advanced and efficacious therapy. Proteins, molecular markers, and genes are some of the theranostic strategies that could be used to amplify the surface of the nanotheranostics particle and make benefit of the features of the micro-environment utilising stimulus-based triggers. The current chapter focused on the theranostic approach of dendrimer for brain tumor treatment. It also enlightened about various diagnostic techniques for brain tumors with a special emphasis on nanotherapeutics. 

Cancer or malignancy is the most widely occurring ailment in the recent scenario. Brain tumor is considered to be one of the most fatal among all types of tumors. The brain-related tumors are numerous and need to be treated and diagnosed in different ways. The diagnosis of brain tumor is done by various methods like MRI, CT scan and neurological testing. In the recent past, a number of nanoemulsion formulations have been formulated and developed to treat and diagnose brain cancer. The present work presents the present status of anti-cancer drugs, the parameters related to their working and the advancement in technology.

Brain cancer is considered one of the most vicious and devastating tumors owing to its poor prognosis and high mortality rate. Common strategies for treatment include surgery, radiation, and chemotherapy. Unfortunately, these are limited due to their invasive nature and the inherent difficulties of brain surgery, given there is a high possibility of tumor relapse. Further, radiation and chemotherapy have a non-selective harmful effect on normal tissues, accompanied by limited drug delivery due to the presence of various barriers, including the blood-brain barrier. For this reason, the theranostic approach was developed by incorporating one or more therapeutic and diagnostic agents in a single nanocarrier moiety which could be modulated at its surface with certain proteins, legend, surface markers, or a stimuli-responsive agent that is capable of selectively targeting the tumor site after passing through the blood-brain barrier. This new field will permit the early and precise detection of cancer tissue, facilitate the process of drug delivery and assist in monitoring treatment outcomes. Micelles are considered one of the most commonly used nanocarriers due to their high stability and loading capacity, along with efficient release controlling properties. This chapter will present brief information about brain anatomy and cancer, and will discuss the main strategies implemented in the diagnosis and treatment of brain cancers. Furthermore, it will introduce the theranostic micelle approach by highlighting micelles types and preparation techniques, as well as explain the different barriers and approaches to targeting.

Brain tumors pose a major threat to human health due to difficult treatment, rapid progression, and poor prognosis, resulting in a terrible fatality rate that has remained high over the years. As arteries have limited drug permeability into brain tumor tissue, the success rate of chemotherapy remains low. Considering the anatomic concerns of brain tumors and the interaction between the blood-brain barrier (BBB) and nano-particles (NPs), nanotechnology is deemed an attractive approach as it has the potential to increase brain drug distribution. Theranostic strategies have also been proposed in recent years and they are seen promising. NPs are considered ideal due to their size, ease of surface modification and, adaptability to integrating several functional components in one system. In lieu of this, the design of nano-particles with therapeutic and diagnostic uses has increased tremendously, particularly in cancer treatment. This two-pronged technique aids in understanding tumor tissue location, treatment progress, nanoparticle’s bio-distribution and, its efficacy as it is particularly valuable for personalized medicine-based treatments. In this chapter, we will focus on the properties of the blood-brain barrier and the blood-brain tumor barrier (BBTB), two important hurdles in brain-tumor targeted delivery, and the targeting strategies that aim at different stages of brain tumor growth and development as well as their recent advances in brain tumor-targeted novel nano-drug delivery systems.