Acid-labile core cross-linked micelles for pH-triggered release of antitumor drugs

被引:170
作者
Chan, Yannie [1 ]
Wong, To [1 ]
Byrne, Frances [2 ]
Kavallaris, Maria [2 ]
Bulmus, Volga [1 ,3 ]
机构
[1] Univ New S Wales, CAMD, Sydney, NSW 2052, Australia
[2] Childrens Canc Inst Australia Med Res, Sydney, NSW 2031, Australia
[3] Univ New S Wales, Sch Biotechnol & Biomol Sci BABS, Sydney, NSW 2052, Australia
关键词
D O I
10.1021/bm800043n
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Micelles of a model amphiphilic block copolymer, poly(hydroxyethyl acrylate)-block-poly(n-butyl acrylate) (PHEA-b-PBA), synthesized via the RAFT polymerization were cross-linked by copolymerization of a degradable crosslinker from the living RAFT-end groups of PBA chains, yielding a cross-linked core without affecting significantly the original micelle size. The cross-linker incorporation into the micelles was, evidenced via physicochemical analysis of the copolymer unimers formed upon acidic cleavage of the cross-linked micelles. High doxorubicin loading capacities (60 wt %) were obtained. Hydrolysis of less than half of the cross-links in the core was found to be sufficient to release doxorubicin faster at acidic pH compared to neutral pH. The system represents the first example of core-cross-linked micelles that can be destabilized (potentially both above and below CMC) by the pH-dependent cleavage of the cross-links and the subsequent polarity change in the core to enable the release of hydrophobic drugs entrapped inside the micelle.
引用
收藏
页码:1826 / 1836
页数:11
相关论文
共 59 条
[1]   Decoration of shell cross-linked reverse polymer micelles using ATRP: A new route to stimuli-responsive nanoparticles [J].
Babin, Jerome ;
Lepage, Martin ;
Zhao, Yue .
MACROMOLECULES, 2008, 41 (04) :1246-1253
[2]   Design of environment-sensitive supramolecular assemblies for intracellular drug delivery: Polymeric micelles that are responsive to intracellular pH change [J].
Bae, Y ;
Fukushima, S ;
Harada, A ;
Kataoka, K .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2003, 42 (38) :4640-4643
[3]   Preparation and biological characterization of polymeric micelle drug carriers with intracellular pH-triggered drug release property: Tumor permeability, controlled subcellular drug distribution, and enhanced in vivo antitumor efficacy [J].
Bae, Y ;
Nishiyama, N ;
Fukushima, S ;
Koyama, H ;
Yasuhiro, M ;
Kataoka, K .
BIOCONJUGATE CHEMISTRY, 2005, 16 (01) :122-130
[4]   ASPECTS OF THE DEGRADATION KINETICS OF DOXORUBICIN IN AQUEOUS-SOLUTION [J].
BEIJNEN, JH ;
VANDERHOUWEN, OAGJ ;
UNDERBERG, WJM .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 1986, 32 (2-3) :123-131
[5]  
Bloch D. R, 2003, POLYM HDB
[6]   Polymer micelles with cross-linked ionic cores for delivery of anticancer drugs [J].
Bontha, Satya ;
Kabanov, Alexander V. ;
Bronich, Tatiana K. .
JOURNAL OF CONTROLLED RELEASE, 2006, 114 (02) :163-174
[7]   Synthesis and characterization of degradable p(HEMA) microgels: Use of acid-labile crosslinkers [J].
Bulmus, Volga ;
Chan, Yannie ;
Nguyen, Quyen ;
Tran, Hong L. .
MACROMOLECULAR BIOSCIENCE, 2007, 7 (04) :446-455
[8]   Acid-cleavable polymeric core-shell particles for delivery of hydrophobic drugs [J].
Chan, Yannie ;
Bulmus, Volga ;
Zareie, M. Hadi ;
Byrne, Frances L. ;
Barner, Leonie ;
Kavallaris, Maria .
JOURNAL OF CONTROLLED RELEASE, 2006, 115 (02) :197-207
[9]   Synthesis of dendron functionalized core cross-linked star polymers [J].
Connal, Luke A. ;
Vestberg, Robert ;
Hawker, Craig J. ;
Qiao, Greg G. .
MACROMOLECULES, 2007, 40 (22) :7855-7863
[10]   ACCUMULATION OF DEGRADATION PRODUCTS OF DOXORUBICIN AND PIRARUBICIN FORMED IN CELL-CULTURE MEDIUM WITHIN SENSITIVE AND RESISTANT CELLS [J].
FIALLO, M ;
LAIGLE, A ;
BORREL, MN ;
GARNIERSUILLEROT, A .
BIOCHEMICAL PHARMACOLOGY, 1993, 45 (03) :659-665