Research Progress in Inorganic Nanomaterials for Modulating the Tumour Microenvironment and Overcoming Chemotherapy Resistance

School of Pharmacy, Chongqing Medical University, Chongqing, China

^* Corresponding author: This email address is being protected from spambots. You need JavaScript enabled to view it.

Abstract

Chemotherapy resistance in tumours is a major cause of treatment failure and poor patient prognosis, and its development is closely linked to abnormal regulation of the tumour microenvironment (TME). The TME exhibits various pathophysiological characteristics, including an acidic environment, hypoxia, a dense extracellular matrix, immunosuppression, and abnormal angiogenesis, which further impede drug delivery, enhance tumour cell adaptability, and facilitate immune evasion, ultimately promoting the development and maintenance of chemotherapy resistance. In recent years, inorganic nanomaterials have emerged as promising tools for overcoming chemotherapy resistance because of their structural stability, tunable physicochemical properties, and versatile surface engineering potential. This review systematically summarises the primary mechanisms by which the TME mediates chemotherapy resistance, with a focus on recent intervention strategies based on inorganic nanomaterials. These include achieving targeted drug delivery in response to acidic or hypoxic microenvironments, degrading the extracellular matrix to improve drug penetration, modulating the tumour immune microenvironment to enhance anti-tumour immune responses, and normalising abnormal tumour vasculature to improve drug accumulation. Finally, this paper discusses the challenges faced by inorganic nanomaterials in terms of biosafety, targeting efficiency, and clinical translation, and outlines their prospects for application in reversing tumour chemotherapy resistance.