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

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

doi:10.1016/j.omto.2022.12.002

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

Mol Ther Oncolytics. 2022 Dec 7:28:182-196. doi: 10.1016/j.omto.2022.12.002. eCollection 2023 Mar 16.

Authors

Sihao Zhu^{1

2

3

4

5}, Ziyuan Li^{1

2

3

4

5}, Dongye Zheng^{1

2

3

4

5}, Yue Yu⁶, Jing Xiang^{1

2

3

4

5}, Xiao Ma⁷, Dongqing Xu⁸, Jiajun Qiu⁹, Ziyu Yang¹⁰, Zhiyi Wang¹¹, Jun Li¹², Hongfang Sun¹, Weiqiang Chen^{13

14}, Xiangxi Meng^{15

16}, Yanye Lu^{1

2

3

5}, Qiushi Ren^{1

3

4

5}

Affiliations

¹ Department of Biomedical Engineering, College of Future Technology, Peking University, Beijing 100871, China.
² Institute of Medical Technology, Peking University Health Science Center, Peking University, Beijing 100191, China.
³ National Biomedical Imaging Center, Peking University, Beijing 100871, China.
⁴ Institute of Biomedical Engineering, Shenzhen Bay Laboratory, Shenzhen 5181071, China.
⁵ Institute of Biomedical Engineering, Peking University Shenzhen Graduate School, Shenzhen 518055, China.
⁶ Beijing National Laboratory for Molecular Sciences (BNLMS), Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
⁷ Research Group Signal Transduction, Department of Psychiatry, Ludwig Maximilian University of Munich, Nussbaumstr.7, 80336 Munich, Germany.
⁸ Department of Pediatric Hematology/Oncology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
⁹ Department of Otolaryngology Head and Neck Surgery, the Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
¹⁰ College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen 518060, China.
¹¹ School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, China.
¹² Laboratory Animal Center, Peking University, Beijing 100871, China.
¹³ Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, Gansu Province, China.
¹⁴ Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Lanzhou 730000, Gansu Province, China.
¹⁵ Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing 100142, China.
¹⁶ NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals, Beijing 100142, China.

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.

Keywords: angiogenesis inhibition; homologous targeting; microRNA delivery; microRNA therapeutics; theranostics.