Near-infrared-II Ag2S quantum dot probes targeting podoplanin enhance immunotherapy in oral squamous cell carcinoma

Honggang Xiong; Shuhui Shao; Yixin Yang; Weiming Wang; Haofeng Xiong; Ying Han; Zijia Wang; Xin Hu; Liujun Zeng; Zhimin Yang; Tong Su

doi:10.1016/j.biopha.2023.116011

Near-infrared-II Ag₂S quantum dot probes targeting podoplanin enhance immunotherapy in oral squamous cell carcinoma

Biomed Pharmacother. 2024 Jan:170:116011. doi: 10.1016/j.biopha.2023.116011. Epub 2023 Dec 29.

Authors

Honggang Xiong¹, Shuhui Shao², Yixin Yang³, Weiming Wang¹, Haofeng Xiong¹, Ying Han¹, Zijia Wang¹, Xin Hu¹, Liujun Zeng¹, Zhimin Yang¹, Tong Su⁴

Affiliations

¹ Department of Oral and Maxillofacial Surgery, Center of Stomatology, Xiangya Hospital, Central South University, Changsha, Hunan, China; Research Center of Oral and Maxillofacial Tumor, Xiangya Hospital, Central South University, Changsha, Hunan, China; Institute of Oral Precancerous Lesions, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China.
² Department of Oral and Maxillofacial Surgery, Center of Stomatology, Xiangya Hospital, Central South University, Changsha, Hunan, China; Research Center of Oral and Maxillofacial Tumor, Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China.
³ Xiangya Stomatological Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China.
⁴ Department of Oral and Maxillofacial Surgery, Center of Stomatology, Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China. Electronic address: sutong@csu.edu.cn.

PMID: 38157644
DOI: 10.1016/j.biopha.2023.116011

Abstract

Partial epithelial-mesenchymal transition (pEMT) plays a vital role in oral squamous cell carcinoma (OSCC) cervical lymph node metastasis and tumor immune escape as an immune barrier. However, targeted interventions for pEMT have yet to be established. In this study, we generated an αPDPN-Ag₂S probe by modifying a Podoplanin(PDPN) monoclonal antibody on the surface of near infrared (NIR)-II Ag₂S quantum dots (QDs) with carboxyl groups through an amide reaction. Then, we evaluated its in vivo targeting ability, therapeutic efficacy of eliminating pEMT using αPDPN-Ag₂S-mediated NIR-II photoimmunotherapy (PIT) and biological safety. Here, we found that pEMT is related to CD8 + T-cell infiltration in our human OSCC tissue microarray. Compared with Pdpn^WT SCC7, the slower growth rate of subcutaneous graft tumors implanted with Pdpn^KD SCC7 was associated with a change in the tumor immune microenvironment (TIM) in an immunocompetent C3H/HeJ mouse model. In vitro, αPDPN-Ag2S plus NIR 808 nm laser irradiation induced SCC7 cell death. In vivo, NIR-II imaging results show that the αPDPN-Ag₂S probe has a good active-targeting ability in a 4-nitroquinoline 1-oxide (4NQO)-induced C57 mouse OSCC model and C3H/HeJ SCC7 subcutaneous graft tumor model. Elimination of pEMT cells by NIR-II αPDPN-Ag₂S probe-mediated PIT significantly reversed the local immunosuppressive tumor microenvironment and enhanced PD-1 immunotherapy efficacy. The safety profiles of αPDPN-Ag₂S in BALB/c mice were also acceptable. Thus, αPDPN-Ag₂S has important clinical translational value in predicting the risk of cervical lymph node metastasis. Importantly, our study proposed a new way to improve the efficacy of tumor immunotherapy.

Keywords: Immunotherapy resistant; Near infrared second region; Oral squamous cell carcinoma; Partial EMT; Photoimmunotherapy.

MeSH terms

Animals
Carcinoma, Squamous Cell* / drug therapy
Cell Line, Tumor
Head and Neck Neoplasms*
Humans
Immunotherapy / methods
Lymphatic Metastasis
Mice
Mice, Inbred C3H
Mouth Neoplasms* / therapy
Quantum Dots*
Squamous Cell Carcinoma of Head and Neck / therapy
Tumor Microenvironment