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Leukocyte-Mediated Combined Targeted Chemo and Gene Therapy for Esophageal Cancer

Poor prognosis of esophageal cancer is associated with limited clinical treatment efficacy and lack of targeted therapies. With advances in nanomedicine, nanoparticle drug delivery systems play increasingly important roles in tumor treatment by enabling the simultaneous delivery of multiple therapeu...

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Published in:ACS applied materials & interfaces 2020-10, Vol.12 (42), p.47330-47341
Main Authors: Jun, Yali, Tang, Zhuang, Luo, Chao, Jiang, Baofei, Li, Xiang, Tao, Mingyue, Gu, Hao, Liu, Lu, Zhang, Zhengwei, Sun, Su’An, Han, Kairong, Yu, Xiaojuan, Song, Xudong, Tao, Guoquan, Chen, Xiaofei, Zhang, Li, Gao, Yong, Wang, Qi-long
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creator Jun, Yali
Tang, Zhuang
Luo, Chao
Jiang, Baofei
Li, Xiang
Tao, Mingyue
Gu, Hao
Liu, Lu
Zhang, Zhengwei
Sun, Su’An
Han, Kairong
Yu, Xiaojuan
Song, Xudong
Tao, Guoquan
Chen, Xiaofei
Zhang, Li
Gao, Yong
Wang, Qi-long
description Poor prognosis of esophageal cancer is associated with limited clinical treatment efficacy and lack of targeted therapies. With advances in nanomedicine, nanoparticle drug delivery systems play increasingly important roles in tumor treatment by enabling the simultaneous delivery of multiple therapeutic agents. We here propose a novel nanovector for targeted combination gene therapy and chemotherapy in esophageal cancer. A novel lipid nanovector (EYLN) was designed to carry the chemotherapy drug doxorubicin (Dox) and small interfering RNA against the lipid anabolic metabolism gene LPCAT1, which we previously showed to be significantly overexpressed in esophageal cancer tissues, and its interference inhibited the proliferation, invasion, and metastasis of esophageal cancer cells. This vector, EYLN-Dox/siLPCAT1, was further coated with leukocyte membranes to obtain mEYLNs-Dox/siLPCAT1. The particle size of the coated nanovector was approximately 136 nm, and the surface zeta potential was −21.18 mV. Compared with EYLNs-Dox/siLPCAT1, mEYLNs-Dox/siLPCAT1 were more easily internalized by esophageal cancer cells due to the LFA-1 highly expressed leukocyte membrane coating and showed significant inhibition of the proliferation, migration, and metastasis of esophageal cancer cells, along with their LPCAT1 expression, through more effective delivery of the drugs. Moreover, the nanovectors showed improved blood circulation time, tissue distribution, tumor targeting, and tumor suppression in a mouse model. Thus, combining chemo and gene therapy with this new nanodelivery system achieved greater therapeutic efficacy, providing a new strategy for the treatment of esophageal cancer.
doi_str_mv 10.1021/acsami.0c15419
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source American Chemical Society:Jisc Collections:American Chemical Society Read & Publish Agreement 2022-2024 (Reading list)
subjects 1-Acylglycerophosphocholine O-Acyltransferase - antagonists & inhibitors
1-Acylglycerophosphocholine O-Acyltransferase - genetics
1-Acylglycerophosphocholine O-Acyltransferase - metabolism
Animals
Antibiotics, Antineoplastic - chemistry
Antibiotics, Antineoplastic - pharmacology
Biological and Medical Applications of Materials and Interfaces
Cell Proliferation - drug effects
Doxorubicin - chemistry
Doxorubicin - pharmacology
Drug Carriers - chemistry
Drug Screening Assays, Antitumor
Esophageal Neoplasms - diagnostic imaging
Esophageal Neoplasms - drug therapy
Esophageal Neoplasms - metabolism
Female
Genetic Therapy
Humans
Leukocytes - drug effects
Leukocytes - pathology
Lipids - chemistry
Mice
Mice, Inbred BALB C
Mice, Nude
Nanoparticles - chemistry
Neoplasms, Experimental - diagnostic imaging
Neoplasms, Experimental - drug therapy
Neoplasms, Experimental - metabolism
Particle Size
RNA, Small Interfering - chemistry
RNA, Small Interfering - pharmacology
Surface Properties
Tumor Cells, Cultured
title Leukocyte-Mediated Combined Targeted Chemo and Gene Therapy for Esophageal Cancer
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