Cancer-targeted PEDF-DNA therapy for metastatic colorectal cancer

Xingting Bao; Jun Zeng; Hai Huang; Cuicui Ma; Lei Wang; Fazhan Wang; Xuelian Liao; Xiangrong Song

doi:10.1016/j.ijpharm.2019.118999

Cancer-targeted PEDF-DNA therapy for metastatic colorectal cancer

Int J Pharm. 2020 Feb 25:576:118999. doi: 10.1016/j.ijpharm.2019.118999. Epub 2019 Dec 29.

Authors

Xingting Bao¹, Jun Zeng¹, Hai Huang¹, Cuicui Ma¹, Lei Wang¹, Fazhan Wang¹, Xuelian Liao², Xiangrong Song³

Affiliations

¹ Department of Critical Care Medicine, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu 610041, China.
² Department of Critical Care Medicine, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu 610041, China. Electronic address: xuelianliao@hotmail.com.
³ Department of Critical Care Medicine, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu 610041, China. Electronic address: songxr@scu.edu.cn.

PMID: 31893541
DOI: 10.1016/j.ijpharm.2019.118999

Abstract

Colorectal cancer (CRC) is a major cause of cancer-related mortality worldwide. Moreover, metastasis is one of the main causes of death in CRC patients. Nanotechnology-based gene therapy has shown significant therapeutic benefits in recent clinical trials for cancer treatment. Recent studies have shown that pigment epithelium-derived factor (PEDF) protein can inhibit tumor growth and metastasis by anti-angiogenesis and pro-apoptosis. In this study, we prepared a PEDF-DNA-loaded liposome for cancer-targeted gene therapy for metastatic CRC using an iRGD peptide. Our results showed that cancer-targeted PEDF-DNA liposomes (R-LP/PEDF) exhibited enhanced inhibitory effects on invasion, migration, and pro-apoptosis of CRC cells in vitro. In addition, it reduced metastasis tumor nodules in lung and prolonged the survival time in a mouse model of metastatic CRC.

Keywords: Cancer targeted; Gene therapy; Metastasis; PEDF-DNA; iRGD.

MeSH terms

Animals
Apoptosis
Cell Line, Tumor
Cell Movement
Cell-Penetrating Peptides / chemistry
Cell-Penetrating Peptides / metabolism*
Colorectal Neoplasms / genetics
Colorectal Neoplasms / metabolism
Colorectal Neoplasms / pathology
Colorectal Neoplasms / therapy*
Eye Proteins / genetics*
Eye Proteins / metabolism
Gene Targeting*
Human Umbilical Vein Endothelial Cells / metabolism
Humans
Lung Neoplasms / genetics
Lung Neoplasms / metabolism
Lung Neoplasms / prevention & control*
Lung Neoplasms / secondary
Male
Mice
Mice, Inbred BALB C
Nerve Growth Factors / genetics*
Nerve Growth Factors / metabolism
Oligopeptides / chemistry
Oligopeptides / metabolism*
Receptors, Immunologic / metabolism
Receptors, Peptide / metabolism
Serpins / genetics*
Serpins / metabolism
Tumor Burden

Substances

Cell-Penetrating Peptides
Eye Proteins
N-end cysteine peptide tumor-homing peptide
Nerve Growth Factors
Oligopeptides
Receptors, Immunologic
Receptors, Peptide
Serpins
arginyl-glycyl-aspartic acid directed cell adhesion receptor
pigment epithelium-derived factor