Near‐Infrared‐Enpowered Nanomotor‐Mediated Targeted Chemotherapy and Mitochondrial Phototherapy to Boost Systematic Antitumor Immunity

• Published in: Advanced healthcare materials 2022-07, Vol.11 (14), p.e2200255-n/a
• Main Authors: Zhang, Xueqing, He, Qian, Sun, Jianfeng, Gong, Hanlin, Cao, Yingui, Duan, Lian, Yi, Shixiong, Ying, Binwu, Xiao, Bo
• Format: Article
• Language: English
• Subjects: Antheraea pernyi silk fibroin; Anticancer properties; Antitumor activity; antitumor immunity; Breast cancer; Cell death; Chemotherapy; Damage patterns; Dendritic cells; Doxorubicin; Glycine; Immune system; Immunity; Immunogenicity; Immunosuppressive agents; Light therapy; Macrophages; Metastases; Mitochondria; mitochondrial phototherapy; nanomotors; Nanoparticles; Nanotechnology devices; Near infrared radiation; Penetration depth; Phenotypes; Photodynamic therapy; Phototherapy; Radiation; Silk; Silk fibroin; Synergistic effect; targeted chemotherapy; Tumor cells; Tumor microenvironment
• ISSN: 2192-2640; 2192-2659
• DOI: 10.1002/adhm.202200255

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. Antheraea pernyi silk fibroin‐capped mesoporous silicon nanoparticles with multiresponsibility are facilely developed to deliver the payloads to specific organelles of tumor cells. These nanomotors can penetrate into the internal tumor tissues, self‐produce oxygen, achieve multimodal image‐guided mitochondrial phototherapy, and further exert synergistic effects on the inhibition of metastatic breast tumors and the potentiation of systematic antitumor immune responses, suggesting their potential application in image‐guided synergistic treatment of metastatic breast cancer.