Smart Nanoformulations for Brain Cancer Theranostics: Challenges and Promises

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.

Keywords: bioengineering; electro-magnetic nanoparticles; exosomes; focused ultrasound; gliomas; theranostics.

Figure 1

Smart nanoengineering approaches to circumvent the blood brain barrier (BBB). (A) Transcellular and paracellular transport pathways. Increased expression of receptors such as transferrin, integrins and LDL receptors facilitate the receptor-mediated uptake of drug-carrying nanoformulations. (B) Cell- and viral-mediated BBB crossing. Various stem cells, neutrophils, and viral vectors can cross the BBB carrying nanomedicine. (C) Physico-chemical (transient) disruption of the BBB. Focused ultrasound can decrease the structural proteins of tight junctions, namely, claudins and occludin. It can also increase the expression of calcium-activated channels for the delivery of nanomedicine. (ASCs: Adipose-derived mesenchymal stem cells; BBB: Blood brain barrier; BM-MSCs: Bone marrow-derived mesenchymal stem cells; LDL: Low-density lipoprotein; MSCs: Mesenchyma stem cells; NSCs: Neural stem cells; KCa: Calcium-activated potassium channels).

Figure 2

Novel nanoplatforms currently under research for neuro-oncology applications. The figure illustrates some of the major categories of nanoplatforms that are currently being researched for improved and effective diagnosis and therapy of brain cancers.