Exosome-like nanoplatform modified with targeting ligand improves anti-cancer and anti-inflammation effects of imperialine.

Abstract

Currently, most anti-cancer therapies are still haunted by serious and deleterious adverse effects. Here, we report a highly biocompatible tumor cell-targeting delivery systems utilizing exosome-like vesicles (ELVs) that delivers a low-toxicity anti-cancer agent imperialine against non-small cell lung cancer (NSCLC). First, we introduced a novel micelle-aided method to efficiently load imperialine into intact ELVs. Then, integrin α3β1-binding octapeptide cNGQGEQc was modified onto ELV platform for tumor targeting as integrin α3β1 is overexpressed on NSCLC cells. This system not only significantly improved imperialine tumor accumulation and retention, but also had extremely low systemic toxicity both in vitro and in vivo. Our discoveries offer new ways to utilize ELV more efficiently for both drug loading and targeting. The solid pharmacokinetics improvement and extraordinary safety of this system also highlight possibilities of alternative long course cancer therapies using similar strategies.

• Authors: Qing Lin, Mengke Qu, Bingjie Zhou, Hirak K Patra, Zihan Sun, Qiong Luo, Wenyu Yang, Yongcui Wu, Yu Zhang, Lin Li, Lang Deng, Leilei Wang, Tao Gong, Qin He, Ling Zhang, Xun Sun, Zhirong Zhang
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 311-312 Pg. 104-116 (10 2019) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 31484040 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier B.V. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Antineoplastic Agents
• Cevanes
• Integrin alpha3
• Ligands
• Oligopeptides
• peiminine

Topics

• Animals
• Anti-Inflammatory Agents (administration & dosage, pharmacokinetics)
• Antineoplastic Agents (administration & dosage, pharmacokinetics)
• Carcinoma, Non-Small-Cell Lung (drug therapy)
• Cell Line
• Cevanes (administration & dosage, pharmacokinetics)
• Exosomes
• Humans
• Integrin alpha3
• Ligands
• Lung Neoplasms (drug therapy)
• Male
• Mice, Inbred BALB C
• Mice, Nude
• Nanostructures (administration & dosage)
• Oligopeptides (administration & dosage, pharmacokinetics)