Blood-stable, Tumor-adaptable Disulfide Bonded MPEG-(Cys)4-PDLLA Micelles for Chemotherapy

Overview

Journal Biomaterials

Specialty Biomedical Engineering

Date 2012 Oct 20

PMID 23079665

Citations 21

Authors

Seung-Young Lee

Sungwon Kim

Jacqueline Y Tyler

Kinam Park

Ji-Xin Cheng

Affiliations

Soon will be listed here.

Abstract

Although targeted delivery mediated by ligand modified or tumor microenvironment sensitive nanocarriers has been extensively pursued for cancer chemotherapy, the efficiency is still limited by premature drug release after systemic administration. Herein we report a highly blood-stable, tumor-adaptable drug carrier made of disulfide (DS) bonded mPEG-(Cys)(4)-PDLLA micelles. Intravenously injected disulfide bonded micelles stably retained doxorubicin in the bloodstream and efficiently delivered the drug to a tumor, with a 7-fold increase of the drug in the tumor and 1.9-fold decrease in the heart, as compared with self-assembled (SA), non-crosslinked mPEG-PDLLA micelles. In vivo administration of disulfide bonded micelles led to doxorubicin accumulation in cancer cell nuclei, which was not observed after administration of self-assembled micelles. With a doxorubicin dose as low as 2 mg/kg, disulfide bonded micelles almost completely suppressed tumor growth in mice.

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