Advances in Translational Research of mRNA Delivery for Cancer Therapy

doi:10.3870/j.issn.1672-0741.25.11.012

Abstract

Abstract: mRNA delivery technology, an emerging strategy for cancer treatment, achieves therapeutic objectives by precisely delivering protein-encoding mRNA into cells to express target proteins. Delivery vehicles include lipid nanoparticles（LNPs）, polymeric nanoparticles, and exosomes. Component optimization and targeted modifications significantly enhance organ- and cell-specific delivery efficiency and facilitate efficient endosomal escape. PTEN mRNA delivered to non-small cell lung cancer cells combined with PD-1 antibody treatment normalizes the immunosuppressive microenvironment and overcomes primary resistance. Intratumoral injection of OX40L mRNA-LNPs into hepatocellular carcinoma cells inhibits tumor growth by activating T-cell immune responses. pH-responsive nanoparticles encapsulating PTEN mRNA delivered to trastuzumab-resistant breast cancer cells block the PI3K/Akt pathway, thereby inhibiting tumor growth. All-trans retinoic acid-modified LNPs-encapsulating mRNA delivered to colorectal cancer cells more effectively penetrates the mucosal barrier, driving T-cell homing to tumor sites. Liposomal delivery of p53 mRNA to ovarian cancer cells restores p53 activity, regulating apoptosis and cell cycle to reverse chemotherapy resistance. However, clinical translation remains hindered by challenges such as suboptimal delivery efficiency, immunogenicity, and personalized production. Future efforts should integrate single-cell omics, novel degradable carriers, and combination immunotherapies to drive breakthroughs for mRNA-based precision cancer therapy.

Key words: mRNA delivery, cancer immunotherapy, lipid nanoparticles （LNPs）, clinical translation

CLC Number:

R730.5

Wen Xinxin, Ma Ziwei, Zeng Lu et al. Advances in Translational Research of mRNA Delivery for Cancer Therapy[J]. Acta Medicinae Universitatis Scientiae et Technologiae Huazhong, 2026, 55(5): 759-764.

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