Multidrug resistance (MDR) remains a formidable barrier to successful cancer treatment, driven by mechanisms such as efflux pump overexpression, enhanced DNA repair, evasion of apoptosis and the protective characteristics of the tumour microenvironment. Nanoparticle-based delivery systems have emerged as promising platforms capable of addressing these challenges by enhancing intracellular drug accumulation, enabling targeted delivery and facilitating stimuli-responsive and controlled release. This review provides a comprehensive overview of the molecular and cellular mechanisms underlying MDR and critically examines recent advances in nanoparticle strategies developed to overcome it. Various nanoparticle designs are analysed in terms of their structural and functional features, including surface modifications, active targeting ligands and responsiveness to tumour-specific cues. Particular emphasis is placed on the co-delivery of chemotherapeutic agents with gene regulators, such as siRNA, and the use of nanoparticles to deliver CRISPR/Cas9 gene editing tools as a means of re-sensitising resistant cancer cells. While significant progress has been made in preclinical settings, challenges such as tumour heterogeneity, limited clinical translation and immune clearance remain. Future directions include the integration of precision nanomedicine, scalable manufacturing and non-viral genome editing platforms. Collectively, nanoparticle-based drug delivery systems offer a multifaceted approach to combat MDR and hold great promise for improving therapeutic outcomes in resistant cancers.
多药耐药性（MDR）是癌症治疗中的主要障碍，其机制包括外排泵过表达、DNA修复增强、凋亡逃逸以及肿瘤微环境的保护特性。基于纳米颗粒的递送系统已成为应对这些挑战的有效平台，能够通过增强细胞内药物积累、实现靶向递送并促进刺激响应与可控释放来克服耐药性。本文系统综述了MDR的分子与细胞机制，并重点评述了近年来为克服MDR而开发的纳米颗粒策略的最新进展。文章从结构与功能特征（包括表面修饰、主动靶向配体及对肿瘤特异性信号的响应能力）分析了多种纳米颗粒设计，特别关注化疗药物与基因调控剂（如siRNA）的联合递送，以及利用纳米颗粒递送CRISPR/Cas9基因编辑工具以恢复耐药癌细胞敏感性的策略。尽管临床前研究已取得显著进展，但肿瘤异质性、临床转化受限及免疫清除等问题依然存在。未来发展方向包括整合精准纳米医学、可规模化制造技术及非病毒基因组编辑平台。总体而言，基于纳米颗粒的药物递送系统为对抗MDR提供了多维度解决方案，在改善耐药癌症治疗效果方面具有广阔前景。
Nanoparticle-Based Delivery Strategies for Combating Drug Resistance in Cancer Therapeutics
肿瘤(癌症)患者之家