김지훈 (Georgia Insititute of Technology)

한빛사논문

조회899

Georgia Insititute of Technology

CV File 281 kb

Nat. Commun., Published 18 March 2022 | https://doi.org/10.1038/s41467-022-29121-x Thermosensitive hydrogel releasing nitric oxide donor and anti-CTLA-4 micelles for anti-tumor immunotherapy

Jihoon Kim^1,2, David M. Francis^1,3, Lauren F. Sestito^4,5, Paul A. Archer^1,3, Margaret P. Manspeaker^1,3, Meghan J. O’Melia^4,5 & Susan N. Thomas^1,2,4,5,6,*

¹Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, 315 Ferst Dr NW, Atlanta, GA 30332, USA. ²George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, 315 Ferst Dr NW, Atlanta, GA 30332, USA. ³School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, 315 Ferst Dr NW, Atlanta, GA 30332, USA. ⁴Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, 313 Ferst Dr NW, Atlanta, GA 30332, USA. ⁵Wallace H. Coulter Department of Biomedical Engineering, Emory University, 201 Dowman Drive, Atlanta, GA 30322, USA. ⁶Winship Cancer Institute, Emory University School of Medicine, 1365-C Clifton Road NE, Atlanta, GA 30322, USA.

^*Corresponding author.

Abstract

Due to their autosynchronous roles in shaping the anti-tumor immune response, complex immune regulatory networks acting both locally within the tumor microenvironment as well as in its draining lymph nodes play critical roles in the cancer immunotherapy response. We describe herein a thermosensitive co-polymer hydrogel system formed from biocompatible polymers gelatin and Pluronic^® F127 that are widely used in humans to enable the sustained release of a nitric oxide donor and antibody blocking immune checkpoint cytotoxic T-lymphocyte-associated protein-4 for efficient and durable anti-tumor immunotherapy. By virtue of its unique gel formation and degradation properties that sustain drug retention at the tumor tissue site for triggered release by the tumor microenvironment and formation of in situ micelles optimum in size for lymphatic uptake, this rationally designed thermosensitive hydrogel facilitates modulation of two orthogonal immune signaling networks relevant to the regulation of the anti-tumor immune response to improve local and abscopal effects of cancer immunotherapy.

논문정보

형식Research article
게재일2022년 03월 (BRIC 등록일 2022-03-24)
연구진국외 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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