Shen Junjian, Lin Minghui, Ding Mengbin, Yu Ningyue, Yang Chun, Kong Deping, Sun Haitao, Xie Zongyu
Department of Radiology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233000, PR China.
Institute of Translational Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 201620, Shanghai, PR China.
Mater Today Bio. 2022 Sep 5;16:100416. doi: 10.1016/j.mtbio.2022.100416. eCollection 2022 Dec.
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 Ca, locally encapsulating the semiconducting polymer nanoparticles (SPN) 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 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.
免疫疗法最近被视为一种抑制肿瘤生长和转移的有前景的治疗手段,然而其疗效受到肿瘤内在免疫抑制微环境的限制。在此,我们报道了一种肿瘤免疫抑制微环境调节水凝胶(TIMmH)平台,以实现联合二次近红外(NIR-II)光热疗法(PTT)的免疫疗法,从而持久抑制乳腺癌。该TIMmH平台是通过将NIR-II光热纳米剂和免疫佐剂胞嘧啶-磷酸-鸟嘌呤寡脱氧核苷酸(CpG ODNs)共负载到海藻酸盐水凝胶(ALG)中合成的。将ALG注入肿瘤后,TIMmH通过与Ca的配位作用原位形成,在胶体中局部包裹半导体聚合物纳米颗粒(SPN)和CpG,从而延长了免疫治疗剂的积累时间,并防止其过早受损和释放。在1064纳米光照射下,TIMmH能够升高肿瘤内温度以消融肿瘤,这可诱导肿瘤细胞凋亡,并通过调节免疫抑制微环境实现热免疫激活。TIMmH介导的联合治疗有效抑制了乳腺癌的生长,甚至对肺转移获得了持续抑制。本研究提供了一种新型的具有NIR-II光激发能力的肿瘤免疫抑制微环境调节水凝胶平台,用于安全、有效且持久地抑制肺转移的乳腺癌治疗。
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