Polymer-based nanomedicines: Supporting multimodal approaches to glioblastoma multiforme treatment

Glioblastoma multiforme (GBM) remains one of the most aggressive and lethal cancers affecting the central nervous system (CNS), with significant obstacles precluding effective diagnosis, treatment, and monitoring including the presence of the blood-brain barrier, tumor heterogeneity, and an immunosuppressive tumor microenvironment. Polymer-based nanomedicines have emerged as a promising approach to overcome these barriers, offering innovative targeted diagnostic and therapeutic strategies for GBM patients. This review provides an overview of why GBM remains a diagnostic and therapeutic challenge and provides a summary of recent high-impact studies that explored how polymers and polypeptides can be employed to promote blood-brain barrier penetration and tumor accumulation and provide positive therapeutic outcomes. We also discuss the use of polymers/polypeptides in the development of multimodal therapies for GBM, including the combination of chemotherapeutic and molecularly targeted drugs/treatments, explore how they support the combination of distinct therapeutic modalities (such as phototherapy and immunotherapy) in a single platform, and describe how they apply to the development of novel GBM theranostic strategies. We then discuss the preclinical validation of polymer-based therapeutic approaches to GBM by exploring recent advances in complex in vitro and in vivo models. Finally, we look to the future of GBM treatment with nanomedicines, describing emerging therapeutic strategies for GBM and how we may boost the clinical translation of often complex polymer-based nanomedicines. Overall, this review provides robust evidence for the relevance of polymer-based nanomedicines in GBM treatment.