A Shear-Thinning Biomaterial-Mediated Immune Checkpoint Blockade

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; Ali Khademhosseini

doi:10.1021/acsami.2c06137

A Shear-Thinning Biomaterial-Mediated Immune Checkpoint Blockade

ACS Appl Mater Interfaces. 2022 Aug 10;14(31):35309-35318. doi: 10.1021/acsami.2c06137. Epub 2022 Aug 1.

Authors

Qingzhi Wu^{1

2}, Moyuan Qu^{1

3}, Han-Jun Kim^{1

4}, Xingwu Zhou^{1

5}, Xing Jiang^{1

6}, Yi Chen¹, Jixiang Zhu^{1

7}, Li Ren^{1

8}, Tyler Wolter⁹, Heemin Kang¹⁰, Chun Xu^{1

11}, Zhen Gu^{12

13

14

15

16

17}, Wujin Sun^{1

4

18}, Ali Khademhosseini^{4

17}

Affiliations

¹ Department of Bioengineering, Center for Minimally Invasive Therapeutics (C-MIT), California NanoSystems Institute, University of California, Los Angeles, Los Angeles, California 90095, United States.
² State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan 430070, P.R. China.
³ 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.
⁴ Terasaki Institute for Biomedical Innovation, Los Angeles, California 90024, United States.
⁵ Department of Pharmaceutic Science, University of Michigan, Ann Arbor, Michigan 48105, United States.
⁶ School of Nursing, Nanjing University of Chinese Medicine, Nanjing 210023, P.R. China.
⁷ The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, School of Biomedical Engineering, Guangzhou 511436, P.R. China.
⁸ Key Laboratory for Space Bioscience and Biotechnology, School of Life Science, Northwestern Polytechnical University, Xi'an 710072, P.R. China.
⁹ Academy of Integrated Science, Virginia Tech, Blacksburg, Virginia 24061, United States.
¹⁰ Department of Materials Science and Engineering, Korea University, Seoul 02841, Republic of Korea.
¹¹ School of Dentistry, The University of Queensland, Brisbane, QLD 4006, Australia.
¹² College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, P.R. China.
¹³ Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, P.R. China.
¹⁴ MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, P.R. China.
¹⁵ Zhejiang Laboratory of Systems & Precision Medicine, Zhejiang University Medical Center, Hangzhou 311121, P.R. China.
¹⁶ Jinhua Institute of Zhejiang University, Jinhua 321299, P.R. China.
¹⁷ Department of Bioengineering, Center for Minimally Invasive Therapeutics (C-MIT), California NanoSystems Institute, Department of Chemical and Biomolecular Engineering, Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, California 90095, United States.
¹⁸ Department of Biological Systems Engineering, Virginia Tech, Blacksburg, Virginia 24061, United States.

PMID: 35913267
DOI: 10.1021/acsami.2c06137

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.

Keywords: cancer immunotherapy; drug delivery; immune checkpoint blockade; shear-thinning biomaterials; sustained release.

MeSH terms

Animals
Biocompatible Materials / pharmacology
CD8-Positive T-Lymphocytes
Humans
Immune Checkpoint Inhibitors*
Melanoma*
Mice
T-Lymphocytes, Cytotoxic
Tumor Microenvironment

Substances

Biocompatible Materials
Immune Checkpoint Inhibitors