The GSH responsive indocyanine green loaded PD-1 inhibitory polypeptide AUNP12 modified MOF nanoparticles for photothermal and immunotherapy of melanoma

Ying Hao; Tailuo Liu; Hao Zhou; Jinrong Peng; Ka Li; Yuwen Chen

doi:10.3389/fbioe.2023.1294074

The GSH responsive indocyanine green loaded PD-1 inhibitory polypeptide AUNP12 modified MOF nanoparticles for photothermal and immunotherapy of melanoma

Front Bioeng Biotechnol. 2023 Oct 19:11:1294074. doi: 10.3389/fbioe.2023.1294074. eCollection 2023.

Authors

Ying Hao^#^{1

2}, Tailuo Liu^#^{2

3}, Hao Zhou², Jinrong Peng⁴, Ka Li¹, Yuwen Chen¹

Affiliations

¹ West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, China.
² Laboratory of Heart Valve Disease, West China Hospital, Sichuan University, Chengdu, China.
³ Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China.
⁴ State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu, China.

^# Contributed equally.

Abstract

Introduction: Photothermal therapy (PTT) holds significant potential for the treatment of malignant tumors. However, conventional single PTT often struggles to effectively inhibit tumor metastasis and recurrence. In this study, we constructed a MOF nanoparticle with a synergistic therapeutic effect combining photothermal and immunotherapy, enabling selective blocking of the PD-1/PD-L1 pathway within the tumor microenvironment. Methods: Firstly, MOF nanoparticles were synthesized using NH₂-TPDC as ligands and Zr⁺⁴ as metal ions. Subsequently, NH₂ was modified to N₃ via azide transfer reagents. Through a copper free catalytic click chemical reaction, the PD-1/PD-L1 blocking agent AUNP-12 functionalized with disulfide bonds of DBCO was covalently introduced into MOF nanoparticles which were then loaded with the photothermal agent indocyanine green (ICG) to successfully obtain uniformly sized and stable ICG-MOF-SS-AUNP12 nanoparticles. Results and discussion: ICG-MOF-SS-AUNP12 exhibited GSH-triggered release of PD-1/PD-L1 blockers while demonstrating potent photothermal effects capable of efficiently killing tumor cells. Under 808 nm near-infrared (NIR) irradiation, ICG-MOF-SS-AUNP12 effectively promoted the maturation of DC cells and activated immune responses. This study presents a novel method for constructing MOF-based nanodrugs and offers new possibilities for the synergistic treatment of tumors involving photothermal combined with immunotherapy.

Keywords: AUNP12; ICG; MOF nanoparticles; immunotherapy; photothermal therapy.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was financially supported by the National Natural Science Foundation of China (32101161, 32101134), Program of Science and Technology Department of Sichuan Province (23NSFSC0884, 2022YFS0203), the Technology Innovation Project of Science and Technology Bureau of Chengdu (2022-YF05-01468-SN, 2022-YF05-01724-SN), Key Research and Development Project of Science & Technology Department of Sichuan Province (2022ZDZX0020), 1⋅3⋅5 project for disciplines of excellence, West China Hospital, Sichuan University (ZYGD21006).