An injectable adhesive hydrogel for photothermal ablation and antitumor immune activation against bacteria-associated oral squamous cell carcinoma

光热治疗 材料科学 免疫系统 癌症研究 致病菌 细菌 微生物学 抗原 化学 生物 免疫学 纳米技术 遗传学
作者
Liya Bai,Meng Yang,Jiaxin Wu,Ran You,Qian Chen,Yuanyuan Cheng,Zhanyin Qian,Xiaoying Yang,Yinsong Wang,Yuanyuan Liu
出处
期刊:Acta Biomaterialia [Elsevier]
卷期号:186: 229-245
标识
DOI:10.1016/j.actbio.2024.07.027
摘要

Pathogenic bacteria are closely associated with the occurrence, development and metastasis of oral squamous cell carcinoma (OSCC). Antibacterial therapy has been considered an enhancement strategy to suppress bacteria-associated tumors and promote anti-tumor immune responses. Herein, we developed an injectable adhesive hydrogel, PNIPAM/DL@TIR, for the in situ photothermal ablation and robust stimulation of antitumor immunity against OSCC colonized by Porphyromonas gingivalis (Pg), one of the major oral pathogenic bacteria. PNIPAM/DL@TIR, composed of poly(N-isopropylacrylamide), demethylated lignin, and TAT peptide-conjugated IR820, was prepared using a simple dissolve-dry-swell solvent exchange method. Upon 808 nm laser irradiation, PNIPAM/DL@TIR exerted photothermal effects to ablate Pg-colonized OSCC and generate dual tumor and bacterial antigens. Owing to its large number of catechol groups, PNIPAM/DL@TIR efficiently captured these antigens to form an in situ antigen repository, thereby eliciting robust and durable antitumor immune responses. Proteomic analysis revealed that the captured antigens comprised both tumor neoantigens and bacterial antigens. The catechol groups endowed PNIPAM/DL@TIR with antioxidant activity, which was also conducive to stimulating antitumor immunity. Altogether, this study develops an injectable adhesive hydrogel and provides a combination strategy for treating bacteria-associated OSCC. STATEMENT OF SIGNIFICANCE: In this study, we developed an injectable adhesive hydrogel, PNIPAM/DL@TIR, for in situ photothermal ablation and robust stimulation of antitumor immunity against OSCC colonized by Porphyromonas gingivalis, one of the major oral pathogenic bacteria. PNIPAM/DL@TIR, which consists of poly(N-isopropylacrylamide), demethylated lignin, and TAT peptide-conjugated IR820 exhibited outstanding photothermal performance. Owing to the presence of catechol groups, PNIPAM/DL@TIR has good bioadhesive properties and can capture protein antigens to form in situ antigen repository, thus initiating robust and long-term antitumor immune responses. In addition, PNIPAM/DL@TIR exhibited strong antioxidant activity that is favorable for promoting antitumor immunity. In the mouse model of OSCC with bacterial infection, PNIPAM/DL@TIR not only ablated the primary tumors upon NIR laser irradiation, but also induced tumor and bacterial vaccination in situ to suppress distant tumors and lung metastasis.
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