Bioreducible Shell-Cross-Linked Hyaluronic Acid Nanoparticles for Tumor-Targeted Drug Delivery
- Authors
- Han, Hwa Seung; Thambi, Thavasyappan; Choi, Ki Young; Son, Soyoung; Ko, Hyewon; Lee, Min Chang; Jo, Dong-Gyu; Chae, Yee Soo; Kang, Young Mo; Lee, Jun Young; Park, Jae Hyung
- Issue Date
- Feb-2015
- Publisher
- AMER CHEMICAL SOC
- Citation
- BIOMACROMOLECULES, v.16, no.2, pp.447 - 456
- Journal Title
- BIOMACROMOLECULES
- Volume
- 16
- Number
- 2
- Start Page
- 447
- End Page
- 456
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/10812
- DOI
- 10.1021/bm5017755
- ISSN
- 1525-7797
- 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.
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