An iRGD-conjugated photothermal therapy-responsive gold nanoparticle system carrying siCDK7 induces necroptosis and immunotherapeutic responses in lung adenocarcinoma

Rui Cai; Meng Wang; Meiyuan Liu; Xiongjie Zhu; Longbao Feng; Zhongjian Yu; Xia Yang; Zhiwu Zhang; Huili Guo; Rui Guo; Yanfang Zheng

doi:10.1002/btm2.10430

An iRGD-conjugated photothermal therapy-responsive gold nanoparticle system carrying siCDK7 induces necroptosis and immunotherapeutic responses in lung adenocarcinoma

Bioeng Transl Med. 2022 Oct 27;8(4):e10430. doi: 10.1002/btm2.10430. eCollection 2023 Jul.

Authors

Rui Cai^{1

2}, Meng Wang^{1

2}, Meiyuan Liu^{1

2}, Xiongjie Zhu^{1

2}, Longbao Feng³, Zhongjian Yu^{1

2}, Xia Yang^{1

2}, Zhiwu Zhang^{1

2}, Huili Guo^{1

2}, Rui Guo³, Yanfang Zheng^{1

2}

Affiliations

¹ Department of Medical Oncology Affiliated Cancer Hospital and Institute of Guangzhou Medical University Guangzhou China.
² State Key Laboratory of Respiratory Disease Guangzhou China.
³ Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Guangdong Provincial Engineering and Technological Research Center for Drug Carrier Development, Department of Biomedical Engineering Jinan University Guangzhou China.

Abstract

Although immunotherapy has improved the clinical treatment of lung adenocarcinoma (LUAD), many tumors have poor responses to immunotherapy. In this study, we confirmed that high expression of Cyclin-Dependent Kinase 7 (CDK7) promoted an immunosuppressive macrophage phenotype and macrophage infiltration in LUAD. Thus, we have developed an internalizing-RGD (iRGD)-conjugated gold nanoparticle (AuNP) system which carries siCDK7 to activate the antitumor immune response. The iRGD-conjugated AuNP/siCDK7 system exhibited good tumor targeting performance and photothermal effects. The AuNP/siCDK7 system with excellent biosafety exerted a significant photothermal antitumor effect by inducing tumor cell necroptosis. Furthermore, the AuNP/siCDK7 system ameliorated the immunosuppressive microenvironment and enhanced the efficacy of anti-PD-1 treatment by increasing CD8+ T cell infiltration and decreasing M2 macrophage infiltration. Hence, this iRGD-conjugated AuNP/siCDK7 system is a potential treatment strategy for lung adenocarcinoma, which exerts its effects by triggering tumor cell necroptosis and immunotherapeutic responses.

Keywords: CDK7; M2 macrophages; gold nanoparticles; lung adenocarcinoma; necroptosis.