bm5017755_si_001.pdf (715.87 kB)
Bioreducible Shell-Cross-Linked Hyaluronic Acid Nanoparticles for Tumor-Targeted Drug Delivery
journal contribution
posted on 2015-02-09, 00:00 authored by Hwa Seung Han, Thavasyappan Thambi, Ki Young Choi, Soyoung Son, Hyewon Ko, Min Chang Lee, Dong-Gyu Jo, Yee Soo Chae, Young Mo Kang, Jun Young Lee, Jae Hyung ParkThe
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.