TY - JOUR
T1 - Intratumoural Delivery of mRNA Loaded on a Cationic Hyper-Branched Cyclodextrin-Based Polymer Induced an Anti-Tumour Immunological Response in Melanoma
AU - Khazaei Monfared, Yousef
AU - Mahmoudian, Mohammad
AU - Zakeri-Milani, Parvin
AU - Cecone, Claudio
AU - Hayashi, Tomoya
AU - Ishii, Ken J
AU - Conde, João
AU - Matencio, Adrián
AU - Trotta, Francesco
N1 -
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).
PY - 2023/7/24
Y1 - 2023/7/24
N2 - 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.
AB - 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.
KW - cyclodextrin-based polymer
KW - immunotherapy
KW - melanoma cancer
KW - mRNA delivery
UR - https://www.scopus.com/pages/publications/85167849608
U2 - 10.3390/cancers15143748
DO - 10.3390/cancers15143748
M3 - Article
C2 - 37509409
SN - 2072-6694
VL - 15
JO - Cancers
JF - Cancers
IS - 14
M1 - 3748
ER -
SDG 3 Good Health and Well-being