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Dual pH-Responsive Shell-Cleavable Polycarbonate Micellar Nanoparticles for in Vivo Anticancer Drug Delivery.

Authors
  • Liu, Shaoqiong1
  • Ono, Robert J2
  • Yang, Chuan1
  • Gao, Shujun1
  • Ming Tan, Jordan Yong1
  • Hedrick, James L2
  • Yang, Yi Yan1
  • 1 Institute of Bioengineering and Nanotechnology , 31 Biopolis Way, The Nanos , 138669 , Singapore. , (Singapore)
  • 2 IBM Almaden Research Center , 650 Harry Road , San Jose , California 95120 , United States. , (United States)
Type
Published Article
Journal
ACS Applied Materials & Interfaces
Publisher
American Chemical Society
Publication Date
Jun 13, 2018
Volume
10
Issue
23
Pages
19355–19364
Identifiers
DOI: 10.1021/acsami.8b01954
PMID: 29757607
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

To exploit tumor and intracellular microenvironments, pH-responsive diblock copolymers of poly(ethylene glycol) and catechol-functionalized polycarbonate with acid-labile acetal bond as the linker are synthesized to prepare micellar nanoparticles that shed the shell at acidic tumor tissues and inside cancer cells, hence accelerating drug release at the target. The pH-dependent cleavage of the shell is demonstrated at pH 5.0 and 6.5 using 1H NMR. Bortezomib (BTZ, an anticancer drug containing a phenylboronic acid group) is conjugated to the polymers through formation of pH-responsive boronate ester bond between boronic acid and catechol in the polymers. Dual pH-responsive bortezomib-polymer conjugates (BTZ-PC) self-assemble into micellar nanoparticles of small size (<110 nm) with narrow size distribution and high drug loading capacity. Acidic pH accelerates BTZ release from BTZ-PC micelles and enhances intracelluar uptake of the micelles, hence increasing in vitro cytotoxicity against human breast cancer cells. More importantly, the BTZ-PC micelles achieve a stronger antitumor effect in a human breast cancer BT-474 xenograft mouse model than free BTZ and mitigate in vivo hepatotoxicity of BTZ. These dual pH-responsive shell-cleavable nanoparticles are a potentially promising carrier for BTZ delivery.

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