MUC1 aptamer-functionalized chitosan nanoparticles: Targeted delivery platforms for synergistic cancer therapy and multidrug resistance overcoming

Int J Biol Macromol. 2025 Jun 25:145514. doi: 10.1016/j.ijbiomac.2025.145514. Online ahead of print.

Abstract

Recent advances in nanomedicine have paved the way for innovative targeted cancer therapies, particularly through the development of multifunctional nanoscale drug delivery systems. MUC1 aptamer-functionalized chitosan nanoparticles have emerged as a promising platform for the precise delivery of therapeutic agents to MUC1-overexpressing tumors. This review article synthesizes recent studies that employ these engineered nanocarriers to enhance therapeutic efficacy and mitigate multidrug resistance (MDR) in various cancer models. The integration of MUC1 aptamers onto chitosan-based nanoparticles significantly improves tumor cell internalization and tumor-specific accumulation, thereby enhancing the cytotoxicity of encapsulated chemotherapeutics such as 5-fluorouracil, SN-38, epirubicin, and docetaxel. Additionally, these systems have been combined with RNA interference agents, photothermal components, and even genome-editing tools to induce synergistic effects, including apoptosis, necroptosis, and immune-mediated cell death. Despite challenges like protein corona formation that can compromise targeting efficiency, the reviewed studies demonstrate notable improvements in drug delivery precision, controlled release under tumor-microenvironment-specific conditions, and effective modulation of MDR mechanisms through suppression of efflux transporters and oncogenic signaling pathways. Collectively, these findings underscore the potential of MUC1 aptamer-functionalized chitosan nanoparticles as a highly adaptable and efficacious strategy for synergistic cancer therapy and MDR reversal, with promising implications for future clinical translation.

Keywords: Chitosan nanoparticles; Controlled release; Gene therapy; MUC1 aptamer; Multidrug resistance; Nanomedicine; Photothermal therapy; Protein corona; Synergistic cancer therapy; Targeted drug delivery.

Publication types

  • Review