Tümör-ilintili makrofajların TLR7/8 agonisti yüklenmiş lipozomlar ile yeniden eğitimi

Cancer is an extremely complicated disease, and even though there have been years of effort in science to understand and Nind a cure, it still is one of the most terminal conditions. Lately, it is more clearly understood that the intricate wiring of the tumor microenvironment is more determinative than the intrinsic cancerous nature of tumor cells, for both disease prognosis and treatment efNiciency. This environment bears many types of non-cancerous cells; such as endothelial cells, Nibroblasts, and immune cells; all of which become heavily inNluenced by the cancer cells through their wiring of the cancer-helping niche. As proved by the success of a cancer staging approach, that utilizes a quantiNication of the inNiltration of cytotoxic T cell populations, and which often offers a more effective staging system than traditional TNM staging for cancer, the low immunogenicity of the tumor microenvironment has been a new focus of target for kinds of therapies, including cytotoxic and immune- system stimulation approaches. One such approach is targeting tumor-associated macrophages, which are highly specialized immune cells in the tumor microenvironment responsible for many biological functions such as proliferation of cancer cells, enhancement of cancer stemness, metastasis, and a low immunogenic proNile around the environment. Amongst many strategies against these cells that have extraordinary polarization and switch-of-function capabilities, polarizing them back to a tumor-Nighting polarization via stimulatory molecules have yielded promising results, with the biggest obstacle of induction of a systemic immune response. Here, we have utilized liposomal encapsulation of a Toll-Like Receptor 7/8 agonist called resiquimod, in order to re-educate THP-1 macrophages that transformed into tumor-associated macrophages, back to an opposite state where they could no longer be allies of cancer cells. We have characterized the liposomes by size and morphology, and obtained a 200nm size. After we showed that this size ensured selective phagocytosis by macrophages; we loaded resiquimod molecules inside the liposomes through remote loading, with a loading efNiciency of 96%. Tumor- associated macrophages that were obtained by HT-29-conditioned media incubation of THP-1 cells were characterized for their polarization state, and were re-educated with resiquimod-encapsulating liposomes. The efNiciency of re-education was assessed by the reversal of tumor-associated polarization's impact on HT-29 cells in proliferation in standard cell culture by coverage assay and in spheroid culture, cell viability by Nlow cytometry, metastatic capabilities by wound-healing assay, and stemness by immunocytochemistry for CD133. Overall, with a limitation of variety of tests to assess biological functions of the re- education, we have obtained promising results for an immunotherapeutic approach of re-educating tumor-associated macrophages in colorectal cancer.