Peritoneal Gene Transfection of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand for Tumor Surveillance and Prophylaxis

Nasha Qiu; Zhen Zhang; Xuyong Wei; Chang Xu; Xiaolong Jia; Kai Wang; Yunqi Chen; Shuai Wang; Renyi Su; Beini Cen; Youqing Shen; Chunying Chen; Yanpeng Liu; Xiao Xu

doi:10.1021/acs.nanolett.3c01568

Peritoneal Gene Transfection of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand for Tumor Surveillance and Prophylaxis

Nano Lett. 2023 Sep 13;23(17):7859-7868. doi: 10.1021/acs.nanolett.3c01568. Epub 2023 Jul 11.

Authors

Nasha Qiu^{1

2

3

4

5}, Zhen Zhang⁶, Xuyong Wei^{1

2

3}, Chang Xu^{1

2}, Xiaolong Jia⁷, Kai Wang^{1

2

3}, Yunqi Chen¹, Shuai Wang^{1

2}, Renyi Su^{1

2}, Beini Cen¹, Youqing Shen⁴, Chunying Chen⁵, Yanpeng Liu¹, Xiao Xu^{1

2

3}

Affiliations

¹ The Center for Integrated Oncology and Precision Medicine, Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China.
² Zhejiang University School of Medicine, Hangzhou 310058, China.
³ The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310053, China.
⁴ Zhejiang Key Laboratory of Smart Biomaterials and College of Chemical and Biological Engineering, Zhejiang Univeristy, Hangzhou 310027, China.
⁵ CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100090, China.
⁶ Zhejiang Longcharm Bio-tech Pharma Co., Ltd. Hangzhou 310027, China.
⁷ Department of Urology, The First Affiliated Hospital of Ningbo University, Ningbo 315010, China.

PMID: 37433066
DOI: 10.1021/acs.nanolett.3c01568

Abstract

Peritoneal metastasis is very common in gastrointestinal, reproductive, and genitourinary tract cancers in late stages or postsurgery, causing poor prognosis, so effective and nontoxic prophylactic strategies against peritoneal metastasis are highly imperative. Herein, we demonstrate the first gene transfection as a nontoxic prophylaxis preventing peritoneal metastasis or operative metastatic dissemination. Lipopolyplexes of TNF-related-apoptosis-inducing-ligand (TRAIL) transfected peritonea and macrophages to express TRAIL for over 15 days. The expressed TRAIL selectively induced tumor cell apoptosis while exempting normal tissue, providing long-term tumor surveillance. Therefore, tumor cells inoculated in the pretransfected peritoneal cavity quickly underwent apoptosis and, thus, barely formed tumor nodules, significantly prolonging the mouse survival time compared with chemotherapy prophylaxis. Furthermore, lipopolyplex transfection showed no sign of toxicity. Therefore, this peritoneal TRAIL-transfection is an effective and safe prophylaxis, preventing peritoneal metastasis.

Keywords: TRAIL gene therapy; metastasis prophylaxis; nonviral gene transfection; peritoneal gene transfection; peritoneal metastasis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis / genetics
Apoptosis Regulatory Proteins* / genetics
Apoptosis Regulatory Proteins* / pharmacology
Ligands
Membrane Glycoproteins / genetics
Membrane Glycoproteins / pharmacology
Mice
Peritoneal Neoplasms* / genetics
Peritoneal Neoplasms* / prevention & control
Receptors, TNF-Related Apoptosis-Inducing Ligand / genetics
TNF-Related Apoptosis-Inducing Ligand / genetics
Transfection
Tumor Necrosis Factor-alpha / genetics

Substances

Apoptosis Regulatory Proteins
Ligands
Membrane Glycoproteins
Tumor Necrosis Factor-alpha
TNF-Related Apoptosis-Inducing Ligand
Receptors, TNF-Related Apoptosis-Inducing Ligand