NO-Driven Janus Nanomotor Enhances T-Cell Infiltration by Reconstructing Tumor-Associated Blood and Lymphatic Vessels

》》文章原文链接：NO-Driven Janus Nanomotor Enhances T-Cell Infiltration by Reconstructing Tumor-Associated Blood and Lymphatic Vessels

》》Journal：Advanced Science

》》相关产品：Axitinib (SJ-MX0354)

》》产品引用描述：

》》Abstract：

The effectiveness of antitumor immunotherapy is limited to immune cell infiltration into solid tumors, primarily via T-cell migration through tumor blood vessels. This study introduces a multifunctional nitric oxide (NO)-driven hollow gold Janus nanomotor (HAM) designed to promote tumor blood vessel normalization and increase T-cell infiltration, thereby enhancing the immune response against tumors. It is revealed that self-generated NO facilitates the penetration of HAM into tumors and increases pericyte coverage of blood vessels, thereby enhancing intratumoral T-cell infiltration. HAMs then induce and capture whole-tumor antigens to enhance T-cell activation as an in situ cancer vaccine. Additionally, vascular endothelial growth factor C (VEGFC) is used in combination to induce functional lymphangiogenesis, aiding dendritic cell (DC) migration of tumor-draining lymph nodes (TDLNs). In B16F10 mice, the proportion of tumor-infiltrating T cells increased from 0.5% to 27.4% while that of mature DCs in TDLNs increased from 4.3% to 16.6%, markedly improving tumor-killing effects. Similar outcomes are observed in 4T1 tumor-bearing mice. Collectively, this study highlights the importance of paving the way for intratumoral infiltration of immune cells via nanomotors, which provides a novel idea for enhancing antitumor immunotherapeutic effects.

》》部分实验数据展示：

Figure 5. VEGFC-RN reconstructs tumor-associated lymphatic vessels to increase lymphatic drainage and promote DC accumulation in TDLNs. G), Representative images of the in vitro tube formation assay after treatment with BSA-RN, free VEGFC, VEGFC-RN, or VEGFC-RN+Axitinib; Scale bar: 50 μm. H), Total lengths of tubes formed after treatment with BSA-RN, free VEGFC, VEGFC-RN, or VEGFC-RN+Axitinib. L), Representative fluorescence micrographs of B16F10 tumor sections after LYVE-1 staining; Scale bar: 100 μm. M), Ex vivo imaging of tumors and LNs after treatment with HAM-RN combined with BSA-RN, free VEGFC, VEGFC-RN, or VEGFC-RN+Axitinib. N), Average fluorescence intensities of LNs after treatment with HAM-RN combined with BSA-RN, free VEGFC, VEGFC-RN, or VEGFC-RN+Axitinib.