Antibody-conjugated polymer nanoparticles for brain cancer

Abstract

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.

Graphical abstract:

Keywords: Antibody; Brain cancer; Conjugation; Nanoformulations; Targeted therapy; Targeting; Tumor.

Fig. 1

Structure of the BBB. Tight junctions between endothelial cells in the BBB (BBB) form a dense network that prevents substances from passing through. These tightly sealed junctions leave no gaps, creating a formidable barrier to the entry of most drugs, which are unable to penetrate the brain tissue due to this highly selective and protective mechanism. As a result, therapeutic agents face significant challenges in crossing the BBB, limiting the effectiveness of many treatments for brain-related conditions and diseases, including brain cancer. Glial cells, such as astrocytes and microglia, are also shown in the diagram

Fig. 2

Types of polymer nanoparticles used as drug delivery vehicles for brain cancer therapy. Image was generated by Biorender

Fig. 3

Interaction of antibody on polymer nanoparticle surface with receptors expressed on the BBB endothelium for uptake of nanoparticles. Images were generated by Biorender. Figure 3a Antibody-conjugated polymer nanoparticle with drug encapsulated in matrix. Antibodies can be conjugated on the surface of a nanoparticle via various chemical interactions like covalent bond formation. Figure 3b Active-targeting mechanism of antibody-conjugated polymer nanoparticles. Nanoparticles can cross the BBB via interactions with specific surface receptors on BBB endothelial cells to reach tumor cells followed by receptor-mediated transcytosis (RMT). Figure 3c Antibodies can also interact with tumor cell receptors, allowing specific targeting. The figure also demonstrates the mechanisms of receptor-mediated endocytosis