Breast cancer is the most common malignancy among women worldwide, and its high heterogeneity, propensity for metastasis, and susceptibility to drug resistance remain major clinical challenges. Traditional chemotherapeutic agents suffer from poor water solubility, extensive systemic distribution, weak targeting capability, severe toxic side effects, and propensity to induce multidrug resistance. Nanoparticle drug delivery systems (NDDS), leveraging their unique size effects, high drug-loading capacity, and ease of functional modification, provide a powerful platform for revolutionizing breast cancer therapeutic strategies. This review summarizes the recent progress in NDDS applications for breast cancer treatment, with emphasis on studies published within the past five years (while incorporating foundational research where necessary for mechanistic understanding) and on three core aspects: enhanced targeting, efficacy enhancement with toxicity reduction, and overcoming multidrug resistance. Through the synergy of passive targeting (enhanced permeability and retention EPR effect) and active targeting (ligand-receptor mediation), NDDS can achieve precise enrichment at tumor sites. Through controlled release, combination therapies (such as chemotherapy-photothermal/photodynamic/immunotherapy), and stimuli-responsive drug release, NDDS significantly enhance therapeutic outcomes while reducing systemic toxicity. Furthermore, through innovative strategies including co-delivery of resistance reversal agents, modulation of the tumor microenvironment (TME), silencing of resistance-related genes, and interference with energy metabolism, NDDS demonstrate substantial potential in reversing multidrug resistance in breast cancer. Finally, this article discusses the challenges facing clinical translation of NDDS and future development directions.
Pan et al. (2026) studied this question.