title: Bioreducible shell-cross-linked hyaluronic acid nanoparticles for tumor-targeted drug delivery.
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.
authors.affiliation: School of Chemical Engineering, College of Engineering, Sungkyunkwan University , Suwon 440-746, Republic of Korea.
authors.forename: Hwa Seung
authors.initials: HS
authors.lastname: Han
authors.forename: Thavasyappan
authors.initials: T
authors.lastname: Thambi
authors.forename: Ki Young
authors.initials: KY
authors.lastname: Choi
authors.forename: Soyoung
authors.initials: S
authors.lastname: Son
authors.forename: Hyewon
authors.initials: H
authors.lastname: Ko
authors.forename: Min Chang
authors.initials: MC
authors.lastname: Lee
authors.forename: Dong-Gyu
authors.initials: DG
authors.lastname: Jo
authors.forename: Yee Soo
authors.initials: YS
authors.lastname: Chae
authors.forename: Young Mo
authors.initials: YM
authors.lastname: Kang
authors.forename: Jun Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Jae Hyung
authors.initials: JH
authors.lastname: Park
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000378:metabolism*; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000378:metabolism*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage / Q000378:metabolism; D004337:Drug Carriers / Q000008:administration & dosage / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000008:administration & dosage / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D004337:Drug Carriers; D004317:Doxorubicin; D006820:Hyaluronic Acid