Abstract
Cervical cancer remains a significant health burden among women worldwide, with drug resistance posing a major obstacle to effective treatment strategies. This review examines the potential of bioorthogonal chemistry-based intelligent nanocarriers in precise drug delivery for overcoming cervical cancer drug resistance. Targeted delivery of estrogen receptor antagonists enables modulation of estrogen signaling pathways, addressing key resistance pathways such as DNA damage repair pathways, cancer stem cells, autophagy, and metabolic reprogramming. Bioorthogonal chemistry reactions, including click chemistry and Staudinger reactions, optimize drug delivery strategies of intelligent nanoparticles (NPs) within the tumor microenvironment (TME), enhancing targeting efficacy and stability. Nanocarriers designed for specific recognition of ERα and ERβ also enable modulation of the tumor microenvironment (TME) and exhibit synergistic potential when combined with immunotherapy to overcome drug resistance. Overcoming translational barriers and integrating multifunctional nanocarriers with immunomodulatory approaches, metabolic regulation, and artificial intelligence-based design may facilitate the development of advanced precision therapies for cervical cancer through the combined application of bioorthogonal chemistry and nanotechnology.