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Intratumoural Delivery of mRNA Loaded on a Cationic Hyper-Branched Cyclodextrin-Based Polymer Induced an Anti-Tumour Immunological Response in Melanoma
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Orientador(es)
Resumo(s)
mRNA technology has demonstrated potential for use as an effective cancer immunotherapy. However, inefficient in vivo mRNA delivery and the requirements for immune co-stimulation present major hurdles to achieving anti-tumour therapeutic efficacy. Therefore, we used a cationic hyper-branched cyclodextrin-based polymer to increase mRNA delivery in both in vitro and in vivo melanoma cancer. We found that the transfection efficacy of the mRNA-EGFP-loaded Ppoly system was significantly higher than that of lipofectamine and free mRNA in both 2D and 3D melanoma cancer cells; also, this delivery system did not show cytotoxicity. In addition, the biodistribution results revealed time-dependent and significantly higher mEGFP expression in complexes with Ppoly compared to free mRNA. We then checked the anti-tumour effect of intratumourally injected free mRNA-OVA, a foreign antigen, and loaded Ppoly; the results showed a considerable decrease in both tumour size and weight in the group treated with OVA-mRNA in loaded Ppoly compared to other formulations with an efficient adaptive immune response by dramatically increasing most leukocyte subtypes and OVA-specific CD8+ T cells in both the spleen and tumour tissues. Collectively, our findings suggest that the local delivery of cationic cyclodextrin-based polymer complexes containing foreign mRNA antigens might be a good and reliable concept for cancer immunotherapy.
Descrição
Funding text 1 This work is the result of a contract for the University of Turin (Italy) for Training (For Y.K.M.) and for A.M. and a RTDA contract from the D.M 1062/2021 (Ministero dell’Università e della Ricerca) for the University of Turin. This research acknowledges support from the Project CH4.0 under the MIUR program “Dipartimenti di Eccellenza 2023–2027”. J.C. acknowledges that they have a contract with the European Research Council—ERC Starting Grant 848325 for financial support. Funding text 2 This research was partially funded by The Italian Ministry of Enterprises and Made in Italy (project acronym CN-RNA) under the PNRR among the initiatives aimed towards creating an integrated system of research and innovation infrastructures (PNRR M4C2 PROJECTS).
Palavras-chave
cyclodextrin-based polymer immunotherapy melanoma cancer mRNA delivery Oncology Cancer Research SDG 3 - Good Health and Well-being