학술논문

Nanoparticle/Engineered Bacteria Based Triple-Strategy Delivery System for Enhanced Hepatocellular Carcinoma Cancer Therapy
Document Type
article
Source
International Journal of Nanomedicine, Vol Volume 19, Pp 3827-3846 (2024)
Subject
hepatocellular carcinoma
engineered bacteria
chemotherapy
immunotherapy
anti-angiogenesis.
Medicine (General)
R5-920
Language
English
ISSN
1178-2013
29762359
Abstract
Meiyang Yang,1,2,* Weijun Chen,1,* Dhanu Gupta,3 Congjin Mei,1 Yang Yang,1 Bingke Zhao,1 Lipeng Qiu,1 Jinghua Chen1 1School of Life Sciences and Health Engineering, Jiangnan University, Wuxi, People’s Republic of China; 2School of Chemical and Material Engineering, Jiangnan University, Wuxi, People’s Republic of China; 3Department of Paediatrics, University of Oxford, Oxford, UK*These authors contributed equally to this workCorrespondence: Lipeng Qiu; Jinghua Chen, School of Life Sciences and Health Engineering, Jiangnan University, Wuxi, 214122, People’s Republic of China, Email qiulp@jiangnan.edu.cn; chenjinghua@jiangnan.edu.cnBackground: New treatment modalities for hepatocellular carcinoma (HCC) are desperately critically needed, given the lack of specificity, severe side effects, and drug resistance with single chemotherapy. Engineered bacteria can target and accumulate in tumor tissues, induce an immune response, and act as drug delivery vehicles. However, conventional bacterial therapy has limitations, such as drug loading capacity and difficult cargo release, resulting in inadequate therapeutic outcomes. Synthetic biotechnology can enhance the precision and efficacy of bacteria-based delivery systems. This enables the selective release of therapeutic payloads in vivo.Methods: In this study, we constructed a non-pathogenic Escherichia coli (E. coli) with a synchronized lysis circuit as both a drug/gene delivery vehicle and an in-situ (hepatitis B surface antigen) Ag (ASEc) producer. Polyethylene glycol (CHO-PEG2000-CHO)-poly(ethyleneimine) (PEI25k)-citraconic anhydride (CA)-doxorubicin (DOX) nanoparticles loaded with plasmid encoded human sulfatase 1 (hsulf-1) enzyme (PNPs) were anchored on the surface of ASEc (ASEc@PNPs). The composites were synthesized and characterized. The in vitro and in vivo anti-tumor effect of ASEc@PNPs was tested in HepG2 cell lines and a mouse subcutaneous tumor model.Results: The results demonstrated that upon intravenous injection into tumor-bearing mice, ASEc can actively target and colonise tumor sites. The lytic genes to achieve blast and concentrated release of Ag significantly increased cytokine secretion and the intratumoral infiltration of CD4/CD8+T cells, initiated a specific immune response. Simultaneously, the PNPs system releases hsulf-1 and DOX into the tumor cell resulting in rapid tumor regression and metastasis prevention.Conclusion: The novel drug delivery system significantly suppressed HCC in vivo with reduced side effects, indicating a potential strategy for clinical HCC therapy. Keywords: hepatocellular carcinoma, engineered bacteria, chemotherapy, immunotherapy, anti-angiogenesis