Emerging biomaterials deliver heat shock protein 90 inhibitors to enhance therapeutic efficacy in cancer therapy

Innovative biomaterial-based drug delivery systems have shown notable promise in the clinical cancer treatment. However, the therapeutic effect for patients remains highly variable, and new strategies urgently need to be developed. Heat shock protein 90 (HSP90) is multifunctional molecular chaperones that are associated with various human diseases, including cancer, inflammation, and protein misfolding disorders. Notably, when combined with biomaterials, they can enable targeted and regulated tumor microenvironments, making progress in cancer treatment in recent years. Herein, the design concepts, therapeutic mechanisms, and synergistic applications of biomaterials combined with HSP90 inhibitors for cancer therapy will be comprehensively introduced. Additionally, this review will focus on the foundational concepts and structural type classification of HSP90 inhibitors, and summarize the application of biomaterials as inhibitor delivery carriers. Further, we systematically analyze the progress of HSP90 nanoinhibitors combined with other therapies for cancer therapy. Finally, we reasonably discuss the challenges inherent to the combined strategy of biomaterials and HSP90 nanoinhibitors, and the development prospects of new technologies in the engineered biomaterials for HSP90, aiming to provide a new paradigm for improving cancer treatment. STATEMENT OF SIGNIFICANCE: Accumulating evidence has demonstrated that heat shock protein 90 (HSP90)-based nanomedicines are emerging as promising platforms for tumor treatment. This review first categorizes the structural types and therapeutic mechanisms of HSP90 inhibitors, then summarizes the design and preparation strategies of various biomaterials conjugated with these inhibitors. Moreover, the applications of HSP90 nanoinhibitors in both monotherapy and rational combination strategies, as well as the present challenges and future directions for biomaterial-HSP90 inhibitor systems, are systematically discussed, providing new insights for nanotechnology-enabled cancer therapy.