Antibody-conjugated polymer nanoparticles for brain cancer

Brain cancer remains a significant global health challenge, affecting over a million individuals worldwide. It includes primary tumors such as gliomas, particularly glioblastoma multiforme (GBM) being one of the most aggressive forms, and secondary brain tumors resulting from metastases of breast or lung cancer. A major obstacle in treating these malignancies is the blood-brain barrier (BBB), which limits effective drug delivery to tumor sites. Nanoparticles have long been explored as versatile drug delivery vehicles due to their potential to improve tumor specificity, penetrate the BBB, and enhance drug bioavailability. To further refine these delivery systems, antibodies have been conjugated to nanoparticles to target specific tumor biomarkers, thereby enhancing therapeutic precision and efficacy. In preclinical studies, antibody-conjugated polymer nanoparticles have demonstrated promising capabilities in achieving both targeted delivery and BBB penetration. This review first outlines the pathophysiology and mechanisms underlying brain cancer. It then discusses how polymer nanoparticles address current therapeutic limitations, particularly in overcoming the BBB and improving pharmacokinetics. Various polymer nanoparticles are explored, including polymeric micelles, dendrimers, nanocapsules, nanospheres, nanogels, and polymersomes, each offering distinct therapeutic advantages. We further examine the impact of surface modification with antibodies to enhance tumor targeting, discussing their physiochemical properties, as well as in vitro and in vivo findings. Finally, the review critically evaluates the current challenges in the development of antibody-conjugated polymer nanoparticles, identifies research gaps, and future directions of this promising field.