Tissue nanotransfection causes tumor regression by its effect on nanovesicle cargo that alters microenvironmental macrophage state
dc.contributor.author | Gordillo, Gayle M. | |
dc.contributor.author | Guda, Poornachander Reddy | |
dc.contributor.author | Singh, Kanhaiya | |
dc.contributor.author | Biswas, Ayan | |
dc.contributor.author | Abouhashem, Ahmed S. | |
dc.contributor.author | Rustagi, Yashika | |
dc.contributor.author | Sen, Abhishek | |
dc.contributor.author | Kumar, Manishekhar | |
dc.contributor.author | Das, Amitava | |
dc.contributor.author | Ghatak, Subhadip | |
dc.contributor.author | Khanna, Savita | |
dc.contributor.author | Sen, Chandan K. | |
dc.contributor.author | Roy, Sashwati | |
dc.contributor.department | Surgery, School of Medicine | |
dc.date.accessioned | 2024-08-01T13:51:29Z | |
dc.date.available | 2024-08-01T13:51:29Z | |
dc.date.issued | 2023 | |
dc.description.abstract | Extracellular vesicles (EVs) are nanovesicles released by all eukaryotic cells. This work reports the first nanoscale fluorescent visualization of tumor-originating vesicles bearing an angiogenic microRNA (miR)-126 cargo. In a validated experimental model of lethal murine vascular neoplasm, tumor-originating EV delivered its miR-126 cargo to tumor-associated macrophages (TAMs). Such delivery resulted in an angiogenic (LYVE+) change of state in TAM that supported tumor formation. Study of the trafficking of tumor-originating fluorescently tagged EV revealed colocalization with TAM demonstrating uptake by these cells. Ex vivo treatment of macrophages with tumor-derived EVs led to gain of tumorigenicity in these isolated cells. Single-cell RNA sequencing of macrophages revealed that EV-borne miR-126 characterized the angiogenic change of state. Unique gene expression signatures of specific macrophage clusters responsive to miR-126-enriched tumor-derived EVs were revealed. Topical tissue nanotransfection (TNT) delivery of an oligonucleotide comprising an anti-miR against miR-126 resulted in significant knockdown of miR-126 in the tumor tissue. miR-126 knockdown resulted in complete involution of the tumor and improved survival rate of tumor-affected mice. This work identifies a novel tumorigenic mechanism that relies on tumorigenic state change of TAM caused by tumor-originating EV-borne angiomiR. This disease process can be effectively targeted by topical TNT of superficial tumors. | |
dc.eprint.version | Final published version | |
dc.identifier.citation | Gordillo GM, Guda PR, Singh K, et al. Tissue nanotransfection causes tumor regression by its effect on nanovesicle cargo that alters microenvironmental macrophage state. Mol Ther. 2023;31(5):1402-1417. doi:10.1016/j.ymthe.2022.11.003 | |
dc.identifier.uri | https://hdl.handle.net/1805/42536 | |
dc.language.iso | en_US | |
dc.publisher | Elsevier | |
dc.relation.isversionof | 10.1016/j.ymthe.2022.11.003 | |
dc.relation.journal | Molecular Therapy | |
dc.rights | Publisher Policy | |
dc.source | PMC | |
dc.subject | Extracellular vesicles | |
dc.subject | Macrophage | |
dc.subject | Single-cell RNA sequencing | |
dc.subject | angiomiRs | |
dc.subject | miR-126 | |
dc.subject | Tumor | |
dc.subject | Hemangioma | |
dc.title | Tissue nanotransfection causes tumor regression by its effect on nanovesicle cargo that alters microenvironmental macrophage state | |
dc.type | Article | |
ul.alternative.fulltext | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10188642/ |