Engineering design of oxaliplatin nanodelivery systems: Overcoming biological barriers toward precision therapy of colorectal cancer.

Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide, and the clinical efficacy of oxaliplatin (OXA), a first-line chemotherapeutic agent for CRC, is significantly limited by insufficient tumor targeting, limited intratumoral drug accumulation, and acquired drug resistance. Recent advances in nanomedicine have enabled the rational design of OXA nanodelivery systems to improve pharmacokinetics, enhance tumor accumulation, and achieve controlled drug release. This review summarizes the molecular mechanisms underlying OXA resistance and tumor biological barriers, and highlights recent advances in nanocarrier engineering strategies, including active targeting, stimuli-responsive delivery, biomimetic systems, and multifunctional combination therapies. These nanoplatforms can improve drug delivery efficiency, overcome tumor biological barriers, enhance antitumor efficacy, and promote precision therapy. Finally, current challenges and future perspectives for the clinical translation of OXA nanomedicines are discussed.