Advanced co-delivery nanocarriers to overcome drug resistance in breast cancer: carrier-mediated synergistic treatment by chemotherapy and gene therapy

Chemoresistance is a primary factor contributing to chemotherapy failure in breast cancer. Combining chemotherapeutic agents with nucleic acids that interfere with drug resistance-related genes can effectively overcome chemoresistance in breast cancer. However, the stark differences in key physicochemical properties such as hydrophobicity versus hydrophilicity and surface charge, along with their divergent pharmacokinetic profiles, significantly compromise the synergistic therapeutic potential. Co-delivery nanocarriers enable the encapsulation of both chemotherapeutic agents and nucleic acids within a single carrier, which facilitates simultaneously and spatiotemporally targeted and controlled delivery and represents a promising strategy for treating chemoresistant breast cancer. This review summarized the progress of polymer, lipid, and inorganic materials used in the co-delivery of chemotherapeutic drugs and nucleic acids, with a focus on major advances achieved over the past decade. The critical challenges in the design and optimization, clinical translation of these co-delivery systems, and insights for future research were also discussed.