한빛사 논문
Qingzhi Wu,† Moyuan Qu,† Han-Jun Kim,† Xingwu Zhou, Xing Jiang, Yi Chen, Jixiang Zhu, Li Ren, Tyler Wolter, Heemin, Kang, Chun Xu, Zhen Gu, Wujin Sun,* and Ali Khademhosseini*
Prof. Q. Wu, Dr. M. Qu, Prof. H-J Kim, Dr. X. Zhou, Prof. X. Jiang, Dr. Y. Chen, Prof. J. Zhu, Prof. L. Ren, Dr. C. Xu, Prof. Z. Gu, Prof. W. Sun, Prof. A. Khademhosseini
Department of Bioengineering, Center for Minimally Invasive Therapeutics (C-MIT), California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA
Prof. Q. Wu
State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan 430070, P. R. China
Dr. M. Qu
Stomatology Hospital, School of Stomatology, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Clinical Research Center of Oral Disease of Zhejiang Province, Zhejiang University, Hangzhou 310006, P. R. China
Prof. H-J Kim, Prof. W. Sun, Prof. A. Khademhosseini
Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90024, USA
Dr. X. Zhou
Department of Pharmaceutic Science, University of Michigan, Ann Arbor, MI 48105 USA
Prof. X. Jiang
School of Nursing, Nanjing University of Chinese Medicine, Nanjing 210023, P. R. China
Prof. J. Zhu
Department of Biomedical Engineering, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, P. R. China
Prof. L. Ren
Key Laboratory for Space Bioscience and Biotechnology, School of Life Science, Northwestern Polytechnical University, Xi’an 710072, P. R. China
T. Wolter
Academy of Integrated Science, Virginia Tech, Blacksburg, VA 24061, USA
Prof. H. Kang
Department of Materials Science and Engineering, Korea University, Seoul 02841, Republic of Korea
Dr. C. Xu
School of Dentistry, The University of Queensland, Brisbane, QLD, 4006, Australia
Prof. Z. Gu
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China
MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China Zhejiang Laboratory of Systems & Precision Medicine, Zhejiang University Medical Center, Hangzhou 311121, China
Jinhua Institute of Zhejiang University, Jinhua 321299, China
Prof. W. Sun
Department of Biological Systems Engineering, Virginia Tech, Blacksburg, VA 24061, USA
Q.W., M.Q., and H.K. contributed equally to this work.
*Corresponding author.
Abstract
Systemic administration of immune checkpoint blockade agents can activate the anticancer activity of immune cells; however, the response varies from patient to patient and presents potential off-target toxicities. Local administration of immune checkpoint inhibitors (ICIs) can maximize therapeutic efficacies while reducing side effects. This study demonstrates a minimally invasive strategy to locally deliver anti-programmed cell death protein 1 (anti-PD-1) with shear-thinning biomaterials (STBs). ICI can be injected into tumors when loaded in STBs (STB-ICI) composed of gelatin and silicate nanoplatelets (Laponite). The release of ICI from STB was mainly affected by the Laponite percentage in STBs and pH of the local microenvironment. Low Laponite content and acidic pH can induce ICI release. In a murine melanoma model, the injection of STB-ICI significantly reduced tumor growth and increased CD8+ T cell level in peripheral blood. STB-ICI also induced increased levels of tumor-infiltrating CD4+ helper T cells, CD8+ cytotoxic T cells, and tumor death. The STB-based minimally invasive strategy provides a simple and efficient approach to deliver ICIs locally.
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