Activatable Mn2+-Armed nanoagonist augments antitumor immunity in colorectal cancer: A NIR-II Photonic neoadjuvant paradigm

Qing Liang; Jiayuan Chen; Shuai Hou; Di Li; Ying Zhu; Ruiqi Li; Lian Chen; Jiao Li; Wei Fu; Shiqiong Lei; Biying Zhang; Xin Zheng; Tao Zhang; Hongwei Duan; Wenshan He; Jinghua Ren

doi:10.1016/j.biomaterials.2023.122206

Activatable Mn²⁺-Armed nanoagonist augments antitumor immunity in colorectal cancer: A NIR-II Photonic neoadjuvant paradigm

Biomaterials. 2023 Sep:300:122206. doi: 10.1016/j.biomaterials.2023.122206. Epub 2023 Jun 16.

Authors

Qing Liang¹, Jiayuan Chen¹, Shuai Hou², Di Li², Ying Zhu¹, Ruiqi Li¹, Lian Chen¹, Jiao Li¹, Wei Fu¹, Shiqiong Lei³, Biying Zhang¹, Xin Zheng¹, Tao Zhang¹, Hongwei Duan⁴, Wenshan He⁵, Jinghua Ren⁶

Affiliations

¹ Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Institute of Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
² School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 70 Nanyang Drive, Singapore, 637457, Singapore.
³ Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
⁴ School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 70 Nanyang Drive, Singapore, 637457, Singapore. Electronic address: hduan@ntu.edu.sg.
⁵ Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. Electronic address: hewenshan@hust.edu.cn.
⁶ Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Institute of Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. Electronic address: jhrenmed@hust.edu.cn.

PMID: 37348325
DOI: 10.1016/j.biomaterials.2023.122206

Abstract

Postoperative recurrence frequently occurs in patients with colorectal cancer (CRC) due to residual microtumors and host cellular immune dysfunction, leading to major setbacks in clinical outcomes and CRC staging. As an increasingly prevalent therapeutic option for CRC patients, neoadjuvant chemoradiotherapy bears unmet challenges of limited tumor targeting and common side effects of gastrointestinal reaction and radiodermatitis. It is highly desirable to develop neoadjuvant treatment paradigms that impart both tumor-targeting accuracy and protection against recurrence of resectable CRC. Here we report a versatile photo-regulated nanoagonist of plasmonic gold blackbody (AuPB) with a polydopamine (PDA) coating carrying manganese ion (Mn²⁺) payloads (AuPB@PDA/Mn). When armed with second near-infrared (NIR-II) light, AuPB@PDA/Mn with broad-band localized surface plasmon resonance generates local hyperthermia and discharges Mn²⁺ ions, which evidently amplify the effects of immunogenic cell death in tumor cells and activate the cyclic GMP-AMP synthase/stimulator of interferon genes pathway in dendritic cells (DCs), hence potentiating the maturation of DC and the secretion of type I interferon in a synergistic way. Matured DCs undertake the task of tumor antigen presentation as the crosstalk to adaptive immunity. As such, the administration of AuPB@PDA/Mn coupled with NIR-II laser irradiation has eminently augmented the infiltration of CD8⁺ T cells as well as the development of memory CD8⁺ T cells in colorectal tumor models, substantiating enhanced immunomodulatory efficacy against primary and recurrent CRC. Our strategy highlights the potency of an integrated NIR-II photothermal and immunoregulatory modality by photo-activate delivery of Mn²⁺ ions, as a neoadjuvant paradigm for presurgical tumor debulking and against postoperative tumor recurrence.

Keywords: Immunogenic cell death; Manganese ions; Nanoagonist; Neoadjuvant therapy; Second near-infrared window; cGAS/STING pathway.

Publication types

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

MeSH terms

CD8-Positive T-Lymphocytes
Cell Line, Tumor
Colorectal Neoplasms* / drug therapy
Humans
Neoadjuvant Therapy
Neoplasm Recurrence, Local
Neoplasms*
Photons