Key Nano-Strategies for Cisplatin Resistance in Advancing Anti-Cancer Therapy

Cisplatin (CDDP) and other platinum-based agents remain cornerstones of cancer therapy. However, drug resistance severely impairs their clinical efficacy and therapeutic potential. Extensive research has identified diverse CDDP resistance mechanisms, broadly categorized as pre-target, on-target, off-target, and post-target resistance. These mechanisms exhibit substantial heterogeneity across patients and tumor types, highlighting the complexity of resistance development. Notably, resistance to other platinum drugs shares similarities with CDDP, presenting a common therapeutic challenge. Leveraging insights into CDDP resistance, personalized therapeutic strategies offer promise to enhance anti-tumor efficacy and overcome platinum resistance. The integration of nanotechnology and precision medicine has emerged as a pivotal frontier in oncology, where nanotechnology-based drug delivery systems (NDDSs) serve as multifunctional vectors for co-delivering CDDP and resistance-modulating agents. These intelligent platforms enable precise targeting and active circumvention of resistance mechanisms. This review comprehensively explores innovative NDDS strategies to overcome CDDP resistance, focusing on pre-target, on-target, off-target, and post-target mechanisms within a precision medicine framework. By synthesizing these advancements, we aim to provide a forward-looking perspective on NDDSs development and their potential to address the persistent challenge of platinum resistance in anti-cancer therapy.