Thavasyappan Thambi (성균관대학교, 현 경희대학교) | 한빛사논문 > 한빛사

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성균관대학교, 현 경희대학교

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Biomacromolecules, 2015 Feb 9;16(2):447-56 | https://doi.org/10.1021/bm5017755 Bioreducible Shell-Cross-Linked Hyaluronic Acid Nanoparticles for Tumor-Targeted Drug Delivery

Hwa Seung Han,^1,† Thavasyappan Thambi,^1,† Ki Young Choi,² Soyoung Son,¹ Hyewon Ko,³ Min Chang Lee,⁴ Dong-Gyu Jo,^5,3 Yee Soo Chae,⁶ Young Mo Kang,⁶ Jun Young Lee,¹ and Jae Hyung Park ^1,3,*

¹School of Chemical Engineering, College of Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea

²Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea

³Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Suwon 440-746, Republic of Korea

⁴Department of Bionanotechnology, Gachon University, Seongnam 461-701, Republic of Korea

⁵College of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea

⁶School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea

^†These authors contributed equally to this paper
^*Corresponding author: correspondence to Jae Hyung Park

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.

논문정보

형식Research article
게재일2015년 02월 (BRIC 등록일 2024-10-14)
연구진국내 연구진
분야 의약학 > 재생의학
피인용횟수120회 이상 인용된 논문

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