State Key Laboratory of Silkworm Genome Biology, College of Sericulture, Textile and Biomass Sciences, Southwest University, Chongqing, 400715, China.
West China Hospital, Sichuan University, Chengdu, 610041, China.
Adv Healthc Mater. 2022 Jul;11(14):e2200255. doi: 10.1002/adhm.202200255. Epub 2022 May 18.
Phototherapy is an important strategy to inhibit tumor growth and activate antitumor immunity. However, the effect of photothermal/photodynamic therapy (PTT/PDT) is restricted by limited tumor penetration depth and unsatisfactory potentiation of antitumor immunity. Here, a near-infrared (NIR)-driven nanomotor is constructed with a mesoporous silicon nanoparticle (MSN) as the core, end-capped with Antheraea pernyi silk fibroin (ApSF) comprising arginine-glycine-aspartate (RGD) tripeptides. Upon NIR irradiation, the resulting ApSF-coated MSNs (DIMs) loading with photosensitizers (ICG derivatives, IDs) and chemotherapeutic drugs (doxorubicin, Dox) can efficiently penetrate into the internal tumor tissues and achieve effective phototherapy. Combined with chemotherapy, a triple-modal treatment (PTT, PDT, and chemotherapy) approach is developed to induce the immunogenic cell death of tumor cells and to accelerate the release of damage-associated molecular patterns. In vivo results suggest that DIMs can promote the maturation of dendritic cells and surge the number of infiltrated immune cells. Meanwhile, DIMs can polarize macrophages from M2 to M1 phenotypes and reduce the percentages of immunosuppressive Tregs, which reverse the immunosuppressive tumor microenvironment and activate systemic antitumor immunity. By achieving synergistic effects on the tumor inhibition and the antitumor immunity activation, DIMs show great promise as new nanoplatforms to treat metastatic breast cancer.
光疗是抑制肿瘤生长和激活抗肿瘤免疫的重要策略。然而，光热/光动力疗法（PTT/PDT）的效果受到肿瘤穿透深度有限和抗肿瘤免疫增强效果不佳的限制。在这里，构建了一种近红外（NIR）驱动的纳米马达，以介孔硅纳米颗粒（MSN）为核心，端接包含精氨酸-甘氨酸-天冬氨酸（RGD）三肽的柞蚕丝素（ApSF）。在近红外照射下，负载光敏剂（ICG 衍生物，IDs）和化疗药物（阿霉素，Dox）的 ApSF 包覆的 MSNs（DIMs）可以有效地穿透内部肿瘤组织并实现有效的光疗。结合化疗，开发了一种三模态治疗（PTT、PDT 和化疗）方法，以诱导肿瘤细胞的免疫原性细胞死亡并加速损伤相关分子模式的释放。体内结果表明，DIMs 可以促进树突状细胞的成熟并增加浸润免疫细胞的数量。同时，DIMs 可以将巨噬细胞从 M2 表型极化为 M1 表型，并降低免疫抑制性 Tregs 的百分比，从而逆转免疫抑制性肿瘤微环境并激活全身抗肿瘤免疫。通过在肿瘤抑制和抗肿瘤免疫激活方面实现协同作用，DIMs 有望成为治疗转移性乳腺癌的新型纳米平台。
