Tumor immunosuppressive microenvironment modulating hydrogels for second near-infrared photothermal-immunotherapy of cancer

Junjian Shen; Minghui Lin; Mengbin Ding; Ningyue Yu; Chun Yang; Deping Kong; Haitao Sun; Zongyu Xie

doi:10.1016/j.mtbio.2022.100416

Tumor immunosuppressive microenvironment modulating hydrogels for second near-infrared photothermal-immunotherapy of cancer

Mater Today Bio. 2022 Sep 5:16:100416. doi: 10.1016/j.mtbio.2022.100416. eCollection 2022 Dec.

Authors

Junjian Shen¹, Minghui Lin², Mengbin Ding³, Ningyue Yu³, Chun Yang⁴, Deping Kong², Haitao Sun⁴, Zongyu Xie¹

Affiliations

¹ Department of Radiology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233000, PR China.
² Institute of Translational Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 201620, Shanghai, PR China.
³ College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, 201620, PR China.
⁴ Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, Department of Cancer, Zhongshan Hospital, Fudan University, Shanghai, 200032, PR China.

Abstract

Immunotherapy has recently been seen as a hopeful therapeutic device to inhibit tumor growth and metastasis, while the curative efficacy is limited by intrinsic immunosuppressive tumor microenvironment. Herein, we reported a tumor immunosuppressive microenvironment modulating hydrogel (TIMmH) platform to achieve second near-infrared (NIR-II) photothermal therapy (PTT) combined immunotherapy for durable inhibition of breast cancer. This TIMmH platform was synthesized through co-loading of NIR-II photothermal nanoagent and an immunoadjuvant cytosine-phosphateguanosine oligodeoxynucleotides (CpG ODNs) into the alginate hydrogel (ALG). Upon the administration of ALG into the tumor, the TIMmH was in situ formed via the coordination effect with Ca²⁺, locally encapsulating the semiconducting polymer nanoparticles (SP_IIN) and CpG in the colloid, achieving to prolong the accumulation time and prevent the premature damage and release of immunotherapeutic agents. Upon 1064-nm photoirradiation, the TIMmH_SD was able to elevate the intratumoral temperature for the ablation of tumors, which could induce the apoptosis of tumor cells and achieve thermal immune activation by regulating of an immunosuppressive microenvironment. The TIMmH-mediated combined treatment effectively suppressed the growths of breast cancers, and even acquired a sustained inhibition of the lung metastasis. This study provides a novel tumor immunosuppressive microenvironment modulating hydrogel platform with NIR-II photoexcited capacity for the safe, effective and durable lung metastasis-inhibiting breast cancer treatment.

Keywords: Breast cancer; Hydrogels; Immunotherapy; Metastasis; Photothermal therapy.