Facile Generation of Tumor-pH-Labile Linkage-Bridged Block Copolymers for Chemotherapeutic Delivery

Chun-Yang Sun; Yang Liu; Jin-Zhi Du; Zhi-Ting Cao; Cong-Fei Xu; Jun Wang

doi:10.1002/anie.201509507

Facile Generation of Tumor-pH-Labile Linkage-Bridged Block Copolymers for Chemotherapeutic Delivery

Angew Chem Int Ed Engl. 2016 Jan 18;55(3):1010-4. doi: 10.1002/anie.201509507. Epub 2015 Dec 3.

Authors

Chun-Yang Sun¹, Yang Liu¹, Jin-Zhi Du², Zhi-Ting Cao³, Cong-Fei Xu³, Jun Wang^{4

5}

Affiliations

¹ The CAS Key laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, 230027, China.
² Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, 30322, USA.
³ Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, 230027, China.
⁴ The CAS Key laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, 230027, China. jwang699@ustc.edu.cn.
⁵ Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, 230027, China. jwang699@ustc.edu.cn.

PMID: 26756443
DOI: 10.1002/anie.201509507

Abstract

Successful bench-to-bedside translation of nanomedicine relies heavily on the development of nanocarriers with superior therapeutic efficacy and high biocompatibility. However, the optimal strategy for improving one aspect often conflicts with the other. Herein, we report a tactic of designing tumor-pH-labile linkage-bridged copolymers of clinically validated poly(D,L-lactide) and poly(ethylene glycol) (PEG-Dlink(m)-PDLLA) for safe and effective drug delivery. Upon arriving at the tumor site, PEG-Dlink(m)-PDLLA nanoparticles will lose the PEG layer and increase zeta potential by responding to tumor acidity, which significantly enhances cellular uptake and improves the in vivo tumor inhibition rate to 78.1% in comparison to 47.8% of the non-responsive control. Furthermore, PEG-Dlink(m)-PDLLA nanoparticles show comparable biocompatibility with the clinically used PEG-b-PDLLA micelle. The improved therapeutic efficacy and safety demonstrate great promise for our strategy in future translational studies.

Keywords: bridged copolymers; clinical translation; drug delivery; nanoparticles; tumor-acidity-responsive.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / administration & dosage
Antineoplastic Agents / therapeutic use*
Cell Line, Tumor
Humans
Hydrogen-Ion Concentration*
Nanoparticles
Neoplasms / chemistry
Neoplasms / drug therapy*
Polymers / chemistry*

Substances

Antineoplastic Agents
Polymers