Targeted Drug Delivery in brain tumors- nanochemistry applications and advances

Background: Despite advances in surgery, radiotherapy and chemotherapy, brain tumors are still a major health issue due to poor prognosis and high mortality rate. The current treatment options suffer limited efficiency. The main barriers to the effective clinical treatment are systemic toxicity of cytotoxic compounds, physical and functional barrier of the blood brain barrier (BBB), and low selectivity of the therapeutic agents to tumor cells. Objective: To review the advances in targeted drug delivery systems and strategies for brain tumors. Methods: We searched the electronic databases of PubMed, EMBASE, Web of Science, BIOSIS Previews, Cambridge Scientific Abstracts, google scholar and additional sources for published and unpublished trials using the set search terms. The date of the most recent search was 20 March 2020. The studies investigating the applications of targeted drug delivery for brain tumors were collected and the most relevant studies were selected for a comprehensive review. Results: Different anticancer agents and nucleic acid-based therapies have been developed and assessed as novel targeted drug delivery techniques for brain tumors. New vehicles include polymeric and liposomal nanoparticles (NPs), wafers, microchips, microparticle-based nanosystems and cells-based vectors. Strong evidence from preclinical and translational studies indicate the great potentials of these NPs-based technologies in brain tumors and improving the therapeutic outcomes. Research is ongoing to develop effective new anticancer agents as well as strategies for BBB modulation and penetration. Conclusions: New targeted drug delivery systems based on stimuli-responsive NPs have shown promising outcomes in brain tumors. Advances in material design and nanochemistry lead to enhanced intracranial concentrations. Non-invasive technologies such as magnetic resonance imaging-guided ultrasound and high-intensity focused ultrasound have been utilized for BBB modulation with higher precision and improved drug delivery performance.