Yang Rulei, Liu Yiran, Yang Ning, Zhang Tian, Hou Jiazhen, He Zongyan, Wang Yutong, Sun Xujie, Shen Jingshan, Jiang Hualiang, Xie Yuanchao, Lang Tianqun
School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China.
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Pharmaceutics. 2024 Apr 22;16(4):570. doi: 10.3390/pharmaceutics16040570.
Colorectal cancer (CRC) ranks as the third most prevalent global malignancy, marked by significant metastasis and post-surgical recurrence, posing formidable challenges to treatment efficacy. The integration of oligonucleotides with chemotherapeutic drugs emerges as a promising strategy for synergistic CRC therapy. The nanoformulation, lipid nanoparticle (LNP), presents the capability to achieve co-delivery of oligonucleotides and chemotherapeutic drugs for cancer therapy. In this study, we constructed lipid nanoparticles, termed as LNP-I-V by microfluidics to co-deliver oligonucleotides miR159 mimics (VDX05001SI) and irinotecan (IRT), demonstrating effective treatment of CRC both in vitro and in vivo. The LNP-I-V exhibited a particle size of 118.67 ± 1.27 nm, ensuring excellent stability and targeting delivery to tumor tissues, where it was internalized and escaped from the endosome with a pH-sensitive profile. Ultimately, LNP-I-V significantly inhibited CRC growth, extended the survival of tumor-bearing mice, and displayed favorable safety profiles. Thus, LNP-I-V held promise as an innovative platform to combine gene therapy and chemotherapy for improving CRC treatment.
结直肠癌（CRC）是全球第三大常见恶性肿瘤，具有显著的转移和术后复发特征，给治疗效果带来了巨大挑战。将寡核苷酸与化疗药物相结合是一种有前景的协同治疗CRC的策略。纳米制剂脂质纳米颗粒（LNP）具有实现寡核苷酸和化疗药物共同递送用于癌症治疗的能力。在本研究中，我们通过微流控技术构建了名为LNP-I-V的脂质纳米颗粒，以共同递送寡核苷酸miR159模拟物（VDX05001SI）和伊立替康（IRT），在体外和体内均显示出对CRC的有效治疗效果。LNP-I-V的粒径为118.67±1.27nm，确保了优异的稳定性和对肿瘤组织的靶向递送，在肿瘤组织中它被内化并以pH敏感的方式从内体中逃逸。最终，LNP-I-V显著抑制了CRC的生长，延长了荷瘤小鼠的生存期，并显示出良好的安全性。因此，LNP-I-V有望成为一种创新平台，将基因治疗和化疗相结合以改善CRC的治疗。
