Bioreducible Shell-Cross-Linked Hyaluronic Acid Nanoparticles
for Tumor-Targeted Drug Delivery
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 Park
10.1021/bm5017755.s001
https://acs.figshare.com/articles/journal_contribution/Bioreducible_Shell_Cross_Linked_Hyaluronic_Acid_Nanoparticles_for_Tumor_Targeted_Drug_Delivery/2198476
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.
2015-02-09 00:00:00
nanoparticle
bioreducible disulfide linkage
PCL
DOX
model anticancer drug
SCC 7 cells
drug release
HA
drug release rate
drug loading efficiency
cancer therapy