Bioreducible Shell-Cross-Linked Hyaluronic Acid Nanoparticles for Tumor-Targeted Drug Delivery

Title
Bioreducible Shell-Cross-Linked Hyaluronic Acid Nanoparticles for Tumor-Targeted Drug Delivery
Authors
최기영한화승Thavasyappan Thambi손소영고혜원이민창조동규채이수강영모이준영박재형
Issue Date
2015-02
Publisher
Biomacromolecules
Citation
VOL 16, NO 2-456
Abstract
The major issues of self-assembled nanoparticles as drug carriers for cancer therapy include biostability and tumor-targetability because the premature drug release from and nonspecific accumulation of the drug-loaded nanoparticles may cause undesirable toxicity to normal organs and lower therapeutic efficacy. In this study, we developed robust and tumor-targeted nanocarriers based on an amphiphilic hyaluronic acid (HA)-polycaprolactone (PCL) block copolymer, in which the HA shell was cross-linked via a bioreducible disulfide linkage. Doxorubicin (DOX), chosen as a model anticancer drug, was effectively encapsulated into the nanoparticles with high drug loading efficiency. The DOX-loaded bioreducible HA nanoparticles (DOX-HA-ss-NPs) greatly retarded the drug release under physiological conditions (pH 7.4), whereas the drug release rate was markedly enhanced in the presence of glutathione, a thiol-containing tripeptide capable of reducing disulfide bonds in the cytoplasm. Furthermore, DOX-HA-ss-NPs could effectively deliver the DOX into the nuclei of SCC7 cells in vitro as well as to tumors in vivo after systemic administration into SCC7 tumor-bearing mice, resulting in improved antitumor efficacy in tumor-bearing mice. Overall, it was demonstrated that bioreducible shell-cross-linked nanoparticles could be used as a potential carrier for cancer therapy.
URI
http://pubs.kist.re.kr/handle/201004/69456
ISSN
1525-7797
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KIST Publication > Article
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