A cancer cell membrane coated, doxorubicin and microRNA co-encapsulated nanoplatform for colorectal cancer theranostics.

IF 5.3 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Molecular Therapy Oncolytics Pub Date : 2023-03-16 DOI:10.1016/j.omto.2022.12.002

Sihao Zhu, Ziyuan Li, Dongye Zheng, Yue Yu, Jing Xiang, Xiao Ma, Dongqing Xu, Jiajun Qiu, Ziyu Yang, Zhiyi Wang, Jun Li, Hongfang Sun, Weiqiang Chen, Xiangxi Meng, Yanye Lu, Qiushi Ren

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引用次数: 2

Abstract

Endogenous microRNAs (miRNA) in tumors are currently under exhaustive investigation as potential therapeutic agents for cancer treatment. Nevertheless, RNase degradation, inefficient and untargeted delivery, limited biological effect, and currently unclear side effects remain unsettled issues that frustrate clinical application. To address this, a versatile targeted delivery system for multiple therapeutic and diagnostic agents should be adapted for miRNA. In this study, we developed membrane-coated PLGA-b-PEG DC-chol nanoparticles (m-PPDCNPs) co-encapsulating doxorubicin (Dox) and miRNA-190-Cy7. Such a system showed low biotoxicity, high loading efficiency, and superior targeting ability. Systematic delivery of m-PPDCNPs in mouse models showed exceptionally specific tumor accumulation. Sustained release of miR-190 inhibited tumor angiogenesis, tumor growth, and migration by regulating a large group of angiogenic effectors. Moreover, m-PPDCNPs also enhanced the sensitivity of Dox by suppressing TGF-β signal in colorectal cancer cell lines and mouse models. Together, our results demonstrate a stimulating and promising m-PPDCNPs nanoplatform for colorectal cancer theranostics.

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肿瘤细胞膜包被、阿霉素和microRNA共包被的结直肠癌治疗纳米平台。

肿瘤中的内源性microRNAs (miRNA)作为癌症治疗的潜在药物目前正在进行详尽的研究。然而，RNase降解、低效和非靶向递送、有限的生物效应以及目前尚不清楚的副作用仍然是阻碍临床应用的未解决问题。为了解决这个问题，多种治疗和诊断药物的多功能靶向递送系统应该适用于miRNA。在这项研究中，我们开发了膜包被的PLGA-b-PEG DC-chol纳米颗粒(m-PPDCNPs)共包被阿霉素(Dox)和miRNA-190-Cy7。该系统具有生物毒性低、负载效率高、靶向性强等特点。在小鼠模型中系统递送m-PPDCNPs显示出异常特异性的肿瘤积累。miR-190的持续释放通过调节大量的血管生成效应物来抑制肿瘤血管生成、肿瘤生长和迁移。此外，在结直肠癌细胞系和小鼠模型中，m-PPDCNPs还通过抑制TGF-β信号增强Dox的敏感性。总之，我们的研究结果为结直肠癌治疗提供了一个令人兴奋和有前途的m-PPDCNPs纳米平台。

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来源期刊

Molecular Therapy Oncolytics Medicine-Oncology

CiteScore

10.90

自引率

3.50%

发文量

152

审稿时长

6 weeks

期刊介绍： Molecular Therapy — Oncolytics is an international, online-only, open access journal focusing on the development and clinical testing of viral, cellular, and other biological therapies targeting cancer.

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