Smart Nanoformulations for Brain Cancer Theranostics: Challenges and Promises

SIMPLE SUMMARY: Brain metastases are amongst the most invasive and lethal cancers. Yet, effective methods for their diagnosis and therapy have remained elusive. While several factors are responsible for this, the primary hurdle has been the absence of an appropriate delivery strategy for the diagnostic/therapeutic agents to the brain. Fortunately, the advent of nanobiotechnology and the advances in bioengineering techniques have provided some hope to circumvent this hurdle. The aim of this review is to evaluate the suitability of novel smart nanobiotechnological approaches in brain cancer therapy. We discuss several state-of-the-art strategies for specific delivery of drugs to brain cancer sites with minimal side effects. We further delineate several classes of nanoplatforms that have generated tremendous interest among contemporary scientists as potential agents for brain cancer therapy. In doing so, the authors hope that the review will serve as a platform for further studies for the discovery of brain cancer strategies. ABSTRACT: Despite their low prevalence, brain tumors are among the most lethal cancers. They are extremely difficult to diagnose, monitor and treat. Conventional anti-cancer strategies such as radio- and chemotherapy have largely failed, and to date, the development of even a single effective therapeutic strategy against central nervous system (CNS) tumors has remained elusive. There are several factors responsible for this. Brain cancers are a heterogeneous group of diseases with variable origins, biochemical properties and degrees of invasiveness. High-grade gliomas are amongst the most metastatic and invasive cancers, which is another reason for therapeutic failure in their case. Moreover, crossing the blood brain and the blood brain tumor barriers has been a significant hindrance in the development of efficient CNS therapeutics. Cancer nanomedicine, which encompasses the application of nanotechnology for diagnosis, monitoring and therapy of cancers, is a rapidly evolving field of translational medicine. Nanoformulations, because of their extreme versatility and manipulative potential, are emerging candidates for tumor targeting, penetration and treatment in the brain. Moreover, suitable nanocarriers can be commissioned for theranostics, a combinatorial personalized approach for simultaneous imaging and therapy. This review first details the recent advances in novel bioengineering techniques that provide promising avenues for circumventing the hurdles of delivering the diagnostic/therapeutic agent to the CNS. The authors then describe in detail the tremendous potential of utilizing nanotechnology, particularly nano-theranostics for brain cancer imaging and therapy, and outline the different categories of recently developed next-generation smart nanoformulations that have exceptional potential for making a breakthrough in clinical neuro-oncology therapeutics.