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Single-ligand dual-targeting irinotecan liposomes: Control of targeting ligand display by pH-responsive PEG-shedding strategy to enhance tumor-specific therapy and attenuate toxicity.

Abstract：

:Along with the malignant proliferation of tumor requiring nutrients, the expression of L-type amino acid transporter 1(LAT1) and amino acid transporter B0,+ (ATB0,+) in cancer cells is up-regulated that can be used as new targets for active targeting of tumor. However, since normal cells also express amino acid transporters in small amounts, traditional ligand-exposure drug delivery systems are potentially toxic to the body. Therefore, we designed a smart-response drug delivery system that buries the tyrosine ligand in PEG hydration layer at normal tissues and exposes the ligand by cleaving the pH-sensitive bond of PEG at the tumor site. Irinotecan (CPT-11) is actively loaded into the inner aqueous phase of liposomes via a copper ion gradient mechanism which has high encapsulation efficiency and stable drug release profile. Smart-response liposomes showed the strongest cytotoxicity and the maximum cellular uptake in vitro, the largest amount of tumor site accumulation and the best antitumor effect in vivo, compared with non-targeted liposomes and non-sensitive liposomes. It is worth noting that smart-response liposomes not only achieved enhanced antitumor effect but also attenuated side effects compared to ligand-exposure liposomes. This provides a smart responsive drug delivery system for precise treatment and shows a good application prospect.

journal_name

Int J Pharm

journal_title

International journal of pharmaceutics

authors

Wang Z,Lin X,Chi D,Xu Z,Lin G,Liu H,Sun J,He Z,Wang Y

doi

10.1016/j.ijpharm.2020.119680

subject

Has Abstract

pub_date

2020-09-25 00:00:00

pages

119680

eissn

0378-5173

issn

1873-3476

pii

S0378-5173(20)30664-5

journal_volume

587

pub_type

杂志文章

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