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: 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
• Journal: Biomacromolecules (Biomacromolecules) Vol. 16 Issue 2 Pg. 447-56 (Feb 09 2015) ISSN: 1526-4602 [Electronic] United States
• PMID: 25565417 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Biocompatible Materials
• Drug Carriers
• Doxorubicin
• Hyaluronic Acid

Topics

• Animals
• Antineoplastic Agents (administration & dosage, metabolism)
• Biocompatible Materials (administration & dosage, metabolism)
• Cell Line, Tumor
• Doxorubicin (administration & dosage, metabolism)
• Drug Carriers (administration & dosage, metabolism)
• Drug Delivery Systems (methods)
• Hyaluronic Acid (administration & dosage, metabolism)
• Mice
• Mice, Nude
• NIH 3T3 Cells
• Nanoparticles (administration & dosage, metabolism)
• Neoplasms (drug therapy, metabolism)
• Xenograft Model Antitumor Assays (methods)