mRNA递送在肿瘤治疗中的转化研究进展*

doi:10.3870/j.issn.1672-0741.25.11.012

摘要/Abstract

摘要： mRNA递送技术作为肿瘤治疗的新兴策略,通过精确递送编码治疗性蛋白的mRNA至细胞,表达出靶蛋白进而达到肿瘤治疗的目的。mRNA递送的材料包括脂质纳米颗粒、聚合物纳米颗粒、外泌体等。通过组分优化和靶向修饰可显著提升器官/细胞特异性递送效率,并实现高效内体逃逸。PTEN mRNA递送至非小细胞肺癌细胞,联合PD-1抗体处理,可逆转免疫抑制微环境并克服原发性耐药。瘤内注射OX40L mRNA-LNPs至肝癌细胞,可通过激活T细胞免疫应答抑制肿瘤生长。pH响应型纳米粒包裹的PTEN mRNA递送至曲妥珠单抗耐药乳腺癌细胞,可阻断PI3K/Akt通路,进而抑制其生长。全反式维甲酸修饰的LNPs包裹的mRNA递送至结直肠癌细胞,可更有效地突破黏膜屏障,驱动T细胞归巢至肿瘤部位。p53 mRNA通过脂质体递送至卵巢癌细胞,可恢复p53活性,调控细胞凋亡和周期,从而逆转化疗抵抗。然而,临床转化仍面临递送效率不足、免疫原性及个体化生产等挑战。未来研究需融合单细胞组学、新型可降解载体及联合免疫疗法,以推动mRNA递送技术在精准肿瘤治疗中的突破性应用。

关键词: mRNA递送, 肿瘤免疫治疗, 脂质纳米颗粒, 临床转化

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

中图分类号:

R730.5

文鑫鑫, 马紫微, 曾璐, 邹先琼. mRNA递送在肿瘤治疗中的转化研究进展^*[J]. 华中科技大学学报（医学版）, 2026, 55(5): 759-764.

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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mRNA递送在肿瘤治疗中的转化研究进展^*

Advances in Translational Research of mRNA Delivery for Cancer Therapy

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