Nanotechnology-enhanced Chimeric Antigen Receptor-T Cell Therapy for Ovarian Cancer

作者：Zhiwei Zheng, He Xu, Dandan Yang, Jing Yin, Ke Si, Hao Ai, Ying Liu · 发表于：Oncology Advances · 年份：2025 · DOI：10.14218/ona.2025.00013 · 研究领域：CAR-T cell therapy research、Virus-based gene therapy research、RNA Interference and Gene Delivery

Chimeric antigen receptor (CAR)-T cell therapy faces significant challenges in treating solid tumors, including immune evasion, suppressive tumor microenvironments, and on-target/off-tumor toxicity, which limit its clinical efficacy. Although it has revolutionized treatment for hematological malignancies, these obstacles hinder its broader application in solid tumors. Nanotechnology offers innovative strategies to address these limitations through enhanced delivery, localization, and control. This review summarizes recent advances in nanotechnology-assisted CAR-T cell therapies for gynecologic cancers, with a particular focus on messenger RNA (mRNA)-based delivery systems, lipid nanoparticles, hydrogels, and external activation techniques such as photothermal and acoustogenetic modulation. The integration of nanotechnology, especially mRNA-based delivery systems, holds transformative potential for overcoming these barriers. mRNA enables transient, non-integrating expression of CARs, meaning the genetic modifications are temporary. This improves safety and allows flexible control over treatment intensity, while rational sequence optimization (e.g., codon usage, guanine-cytosine content, secondary structure) enhances mRNA stability and protein translation efficiency. Lipid nanoparticles, the leading delivery platform, can be engineered for cell-type specificity and tissue targeting through modulation of their components and surface functionalization. Recent innovations, includi...