与病原菌的发生密切相关,口腔鳞状细胞癌(OSCC)的发展和转移。抗菌治疗被认为是抑制细菌相关肿瘤和促进抗肿瘤免疫反应的增强策略。在这里,我们开发了一种可注射的粘合剂水凝胶,PNIPAM/DL@TIR,用于原位光热消融和针对牙龈卟啉单胞菌(Pg)定植的OSCC的抗肿瘤免疫的强大刺激,口腔主要致病菌之一。PNIPAM/DL@TIR,由聚(N-异丙基丙烯酰胺)组成,去甲基化木质素,和TAT肽缀合的IR820是使用简单的溶解-干燥-溶胀溶剂交换法制备的。在808nm激光照射下,PNIPAM/DL@TIR施加光热效应以消融Pg定植的OSCC并产生双重肿瘤和细菌抗原。由于其大量的儿茶酚基团,PNIPAM/DL@TIR有效地捕获这些抗原以形成原位抗原库,从而引发强大而持久的抗肿瘤免疫反应。蛋白质组学分析显示捕获的抗原包含肿瘤新抗原和细菌抗原。邻苯二酚基团赋予PNIPAM/DL@TIR抗氧化活性,这也有利于刺激抗肿瘤免疫力。总之,这项研究开发了一种可注射粘合剂水凝胶,并为治疗细菌相关性OSCC提供了一种组合策略.重要声明:在这项研究中,我们开发了一种可注射的粘合剂水凝胶,PNIPAM/DL@TIR,用于原位光热消融和针对牙龈卟啉单胞菌定植的OSCC的抗肿瘤免疫的强大刺激,口腔主要致病菌之一。PNIPAM/DL@TIR,由聚(N-异丙基丙烯酰胺)组成,去甲基化木质素,和TAT肽缀合的IR820表现出优异的光热性能。由于儿茶酚基团的存在,PNIPAM/DL@TIR具有良好的生物粘附特性,可以捕获蛋白质抗原以形成原位抗原库,从而启动强大和长期的抗肿瘤免疫反应。此外,PNIPAM/DL@TIR表现出较强的抗氧化活性,有利于提高抗肿瘤免疫力。在细菌感染的OSCC小鼠模型中,PNIPAM/DL@TIR不仅消融了NIR激光照射后的原发肿瘤,还可以诱导肿瘤和细菌原位接种以抑制远处肿瘤和肺转移。
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.