석정수 (Johns Hopkins University School of Medicine)

한빛사논문

조회930

Johns Hopkins University School of Medicine

CV File 168 kb

ACS Nano, Publication Date (Web): December 21, 2018 | DOI: 10.1021/acsnano.8b05399 Hypoxia-tropic Protein Nanocages for Modulation of Tumor- and Chemotherapy-Associated Hypoxia

Xinglu Huang^†‡§¶, Jie Zhuang^⊥¶, Seung Woo Chung^‡§¶ , Buwei Huang^‡▽, Gilad Halpert^‡§, Karina Negron^‡∥, Xuanrong Sun^‡#&, Jun Yang^‡#, Yumin Oh^‡□, Paul M. Hwang^⊥, Justin Hanes^{*‡§▽∥#○}, and Jung Soo Suk^*‡§

^† Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, and State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China
^‡ Center for Nanomedicine, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, United States
^§ Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, United States
^⊥ Cardiovascular Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, United States
^▽ Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, United States
^∥ Department of Pharmacology & Molecular Sciences, Johns Hopkins University, Baltimore, Maryland 21218, United States
^# Department of Chemical & Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland 21218, United States
^& Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, China
^□ The Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, United States
^○ Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, United States

^*Corresponding Authors

Author Contributions
^¶X. Huang, J. Zhuang, and S. W. Chung contributed equally to this work.

Abstract

Despite its central role in tumor progression and treatment resistance, poor vascularization that necessitates penetration of therapeutics through tumor extracellular matrix (ECM) constitutes a significant challenge to managing tumor hypoxia via conventional systemic treatment regimens. In addition, methods to target hypoxic tumor cells are lacking. Here, we discovered that human ferritin nanocages (FTn) possess an intrinsic ability to preferentially engage with hypoxic tumor tissues, in addition to normoxic tumor areas. We also developed a simple method of endowing FTn with spatially controlled “mosaic” surface poly(ethylene glycol) (PEG) coatings that facilitate deep penetration of FTn through ECM to reach hypoxic tumor tissues while retaining its inherent hypoxia-tropic property. Hypoxia-inhibiting agents systemically delivered via this surface-PEGylated FTn were readily accumulated in hypoxic tumor tissues, thereby providing significantly enhanced therapeutic benefits compared to the identical agents delivered in solution as a stand-alone therapy or an adjuvant to restore efficacy of conventional systemic chemotherapy.

Keywords: drug resistance; ferritin nanocage; HIF-1α; hypoxia; PEGylation; tumor penetration

논문정보

형식Research article
게재일2018년 12월 (BRIC 등록일 2019-01-15)
연구진국외 연구진
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