Self-assembled peptide-paclitaxel nanoparticles for enhancing therapeutic efficacy in colorectal cancer

Chemotherapy is one of the main treatments for colorectal cancer, but systemic toxicity severely limits its clinical use. Packaging hydrophobic chemotherapeutic drugs in targeted nanoparticles greatly improve their efficacy and reduce side effects. We previously identified a novel colorectal cancer...

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Main Authors: Lidan Hou, Ting Zhong, Peng Cheng, Bohan Long, Leilei Shi, Xiangjun Meng, Han Yao
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-09-01
Series:Frontiers in Bioengineering and Biotechnology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fbioe.2022.938662/full
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author Lidan Hou
Lidan Hou
Lidan Hou
Ting Zhong
Ting Zhong
Ting Zhong
Peng Cheng
Peng Cheng
Bohan Long
Bohan Long
Bohan Long
Leilei Shi
Xiangjun Meng
Xiangjun Meng
Xiangjun Meng
Han Yao
Han Yao
Han Yao
author_facet Lidan Hou
Lidan Hou
Lidan Hou
Ting Zhong
Ting Zhong
Ting Zhong
Peng Cheng
Peng Cheng
Bohan Long
Bohan Long
Bohan Long
Leilei Shi
Xiangjun Meng
Xiangjun Meng
Xiangjun Meng
Han Yao
Han Yao
Han Yao
author_sort Lidan Hou
collection DOAJ
description Chemotherapy is one of the main treatments for colorectal cancer, but systemic toxicity severely limits its clinical use. Packaging hydrophobic chemotherapeutic drugs in targeted nanoparticles greatly improve their efficacy and reduce side effects. We previously identified a novel colorectal cancer specific binding peptide P-LPK (LPKTVSSDMSLN) from phage display peptide library. Here we designed a self-assembled paclitaxel (PTX)-loaded nanoparticle (LPK-PTX NPs). LPK-PTX NPs displayed a superior intracellular internalization and improved tumor cytotoxicity in vitro. Cy5.5-labeled LPK-PTX NPs showed much higher tumor accumulation in colorectal cancer-bearing mice. Furthermore, LPK-PTX NPs exhibit enhanced antitumor activity and decreased systemic toxicity in colorectal cancer patient-derived xenografts (PDX) model. The excellent in vitro and in vivo antitumor efficacy proves the improved targeting drug delivery, suggesting that peptide P-LPK has potential to provide a novel approach for enhanced drug delivery with negligible systemic toxicity.
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spelling doaj.art-1cd2e0695fc043e798b7d8e32da1f3a82022-12-22T03:49:10ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852022-09-011010.3389/fbioe.2022.938662938662Self-assembled peptide-paclitaxel nanoparticles for enhancing therapeutic efficacy in colorectal cancerLidan Hou0Lidan Hou1Lidan Hou2Ting Zhong3Ting Zhong4Ting Zhong5Peng Cheng6Peng Cheng7Bohan Long8Bohan Long9Bohan Long10Leilei Shi11Xiangjun Meng12Xiangjun Meng13Xiangjun Meng14Han Yao15Han Yao16Han Yao17Department of Gastroenterology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaThe Digestive Disease Research and Clinical Transformation Center, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory of Gut Microecology and Associated Diseases, Shanghai, ChinaDepartment of Gastroenterology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaThe Digestive Disease Research and Clinical Transformation Center, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory of Gut Microecology and Associated Diseases, Shanghai, ChinaDepartment of Gastroenterology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Gastroenterology, Hainan West Central Hospital, Hainan, ChinaDepartment of Gastroenterology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaThe Digestive Disease Research and Clinical Transformation Center, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory of Gut Microecology and Associated Diseases, Shanghai, ChinaThe Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, ChinaDepartment of Gastroenterology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaThe Digestive Disease Research and Clinical Transformation Center, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory of Gut Microecology and Associated Diseases, Shanghai, ChinaDepartment of Gastroenterology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaThe Digestive Disease Research and Clinical Transformation Center, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory of Gut Microecology and Associated Diseases, Shanghai, ChinaChemotherapy is one of the main treatments for colorectal cancer, but systemic toxicity severely limits its clinical use. Packaging hydrophobic chemotherapeutic drugs in targeted nanoparticles greatly improve their efficacy and reduce side effects. We previously identified a novel colorectal cancer specific binding peptide P-LPK (LPKTVSSDMSLN) from phage display peptide library. Here we designed a self-assembled paclitaxel (PTX)-loaded nanoparticle (LPK-PTX NPs). LPK-PTX NPs displayed a superior intracellular internalization and improved tumor cytotoxicity in vitro. Cy5.5-labeled LPK-PTX NPs showed much higher tumor accumulation in colorectal cancer-bearing mice. Furthermore, LPK-PTX NPs exhibit enhanced antitumor activity and decreased systemic toxicity in colorectal cancer patient-derived xenografts (PDX) model. The excellent in vitro and in vivo antitumor efficacy proves the improved targeting drug delivery, suggesting that peptide P-LPK has potential to provide a novel approach for enhanced drug delivery with negligible systemic toxicity.https://www.frontiersin.org/articles/10.3389/fbioe.2022.938662/fullpeptideself-assembledtargeted therapynanoparticlescolorectal cancer
spellingShingle Lidan Hou
Lidan Hou
Lidan Hou
Ting Zhong
Ting Zhong
Ting Zhong
Peng Cheng
Peng Cheng
Bohan Long
Bohan Long
Bohan Long
Leilei Shi
Xiangjun Meng
Xiangjun Meng
Xiangjun Meng
Han Yao
Han Yao
Han Yao
Self-assembled peptide-paclitaxel nanoparticles for enhancing therapeutic efficacy in colorectal cancer
Frontiers in Bioengineering and Biotechnology
peptide
self-assembled
targeted therapy
nanoparticles
colorectal cancer
title Self-assembled peptide-paclitaxel nanoparticles for enhancing therapeutic efficacy in colorectal cancer
title_full Self-assembled peptide-paclitaxel nanoparticles for enhancing therapeutic efficacy in colorectal cancer
title_fullStr Self-assembled peptide-paclitaxel nanoparticles for enhancing therapeutic efficacy in colorectal cancer
title_full_unstemmed Self-assembled peptide-paclitaxel nanoparticles for enhancing therapeutic efficacy in colorectal cancer
title_short Self-assembled peptide-paclitaxel nanoparticles for enhancing therapeutic efficacy in colorectal cancer
title_sort self assembled peptide paclitaxel nanoparticles for enhancing therapeutic efficacy in colorectal cancer
topic peptide
self-assembled
targeted therapy
nanoparticles
colorectal cancer
url https://www.frontiersin.org/articles/10.3389/fbioe.2022.938662/full
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