Precisely Targeted Nano-Controller of PD-L1 Level for Non-Small Cell Lung Cancer Spinal Metastasis Immunotherapy

Lei Zhou; Haifeng Liang; Yuxiang Ge; Wang Ding; Qing Chen; Taiwei Zhang; Lan Xiao; Yulin Li; Jian Dong; Xiaowen He; Fengfeng Xue; Libo Jiang

doi:10.1002/adhm.202200938

Precisely Targeted Nano-Controller of PD-L1 Level for Non-Small Cell Lung Cancer Spinal Metastasis Immunotherapy

Adv Healthc Mater. 2022 Oct;11(20):e2200938. doi: 10.1002/adhm.202200938. Epub 2022 Aug 11.

Authors

Lei Zhou^{1

2}, Haifeng Liang^{1

2}, Yuxiang Ge³, Wang Ding³, Qing Chen^{1

2

4}, Taiwei Zhang^{1

2

4}, Lan Xiao⁵, Yulin Li⁶, Jian Dong^{1

2

7}, Xiaowen He⁷, Fengfeng Xue⁴, Libo Jiang^{1

2}

Affiliations

¹ Department of Orthopaedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, P. R. China.
² Cancer center, Zhongshan Hospital, Fudan University, Shanghai, 200032, P. R. China.
³ Department of Orthopaedics Surgery, Minhang Hospital, School of Materials Science and Engineering, Fudan University, Shanghai, 200237, P. R. China.
⁴ Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, P. R. China.
⁵ Centre for Biomedical Technologies, School of Mechanical, Medical and Process Engineering, Queensland University of Technology, Brisbane, 4059, Australia.
⁶ The Key Laboratory for Ultrafine Materials of Ministry of Education, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Engineering Research Center for Biomedical Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai, 200237, P. R. China.
⁷ Department of Orthopaedic Surgery, Zhongshan Hospital Wusong Branch, Fudan University, Shanghai, 200940, P. R. China.

PMID: 35904523
DOI: 10.1002/adhm.202200938

Abstract

Although immune checkpoint inhibitors (ICIs) have been widely applied to treat non-small cell lung cancer (NSCLC), a significant proportion of patients, especially those with spinal metastasis (NSCLC-SM), are insensitive to anti-programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) ICIs. A drug delivery nano-controller of PD-L1 that targets NSCLC-SM can solve this problem, however, none have been developed to date. In this study, it is shown that integrin β3 (β3-int) is strongly upregulated in NSCLC-SM. Its inhibitor RGDyK promotes PD-L1 ubiquitination, indicating the potential application of RGDyK as a new PD-L1 inhibitor in nano-controller and a targeting peptide for NSCLC-SM treatment. According to the synergistic effect of photodynamic therapy and ICIs on T-cell activation through the release of tumor antigens, RGDyK-modified and zinc protoporphyrin (ZnPP)-loaded mesoporous silicon nanoparticles (ZnPP@MSN-RGDyK) are fabricated. The ZnPP@MSN-RGDyK nanoparticles precisely target β3-int to inhibit PD-L1, exhibiting high photodynamic therapy efficiency, and excellent immunotherapeutic effects in an NSCLC-SM mouse model. Collectively, the findings indicate that ZnPP@MSN-RGDyK is a promising immunotherapeutic agent for treating NSCLC-SM.

Keywords: immunotherapy; integrin β3; nanocapsules; non-small cell lung cancer spinal metastasis; programmed death ligand 1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antigens, Neoplasm / therapeutic use
B7-H1 Antigen / metabolism
B7-H1 Antigen / therapeutic use
Carcinoma, Non-Small-Cell Lung* / drug therapy
Carcinoma, Non-Small-Cell Lung* / metabolism
Immune Checkpoint Inhibitors
Immunotherapy
Integrin beta3 / therapeutic use
Lung Neoplasms* / drug therapy
Lung Neoplasms* / metabolism
Mice
Programmed Cell Death 1 Receptor / metabolism
Programmed Cell Death 1 Receptor / therapeutic use
Silicon
Spinal Neoplasms* / drug therapy

Substances

B7-H1 Antigen
Immune Checkpoint Inhibitors
Programmed Cell Death 1 Receptor
Integrin beta3
Silicon
Antigens, Neoplasm