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Plasmid DNA ionisable lipid nanoparticles as non-inert carriers and potent immune activators for cancer immunotherapy.
- Source :
-
Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2024 May; Vol. 369, pp. 251-265. Date of Electronic Publication: 2024 Mar 29. - Publication Year :
- 2024
-
Abstract
- Immunotherapy is currently a standard of care in the treatment of many malignancies. However, predictable side effects caused by systemic administration of highly immunostimulatory molecules have been a serious concern within this field. Intratumoural expression or silencing of immunogenic and immunoinhibitory molecules using nucleic acid-based approaches such as plasmid DNA (pDNA) and small interfering RNA (siRNA), respectively, could represent a next generation of cancer immunotherapy. Here, we employed lipid nanoparticles (LNPs) to deliver either non-specific pDNA and siRNA, or constructs targeting two prominent immunotherapeutic targets OX40L and indoleamine 2,3-dioxygenase-1 (IDO), to tumours in vivo. In the B16F10 mouse model, intratumoural delivery of LNP-formulated non-specific pDNA and siRNA led to strong local immune activation and tumour growth inhibition even at low doses due to the pDNA immunogenic nature. Replacement of these non-specific constructs by pOX40L and siIDO resulted in more prominent immune activation as evidenced by increased immune cell infiltration in tumours and tumour-draining lymph nodes. Consistently, pOX40L alone or in combination with siIDO could prolong overall survival, resulting in complete tumour regression and the formation of immunological memory in tumour rechallenge models. Our results suggest that intratumoural administration of LNP-formulated pDNA and siRNA offers a promising approach for cancer immunotherapy.<br />Competing Interests: Declaration of competing interest The authors have declared that no competing interest exists.<br /> (Copyright © 2023. Published by Elsevier B.V.)
- Subjects :
- Animals
Mice
Indoleamine-Pyrrole 2,3,-Dioxygenase genetics
Female
Cell Line, Tumor
Melanoma, Experimental therapy
Melanoma, Experimental immunology
Lipids chemistry
Lipids administration & dosage
Drug Carriers chemistry
Immunotherapy methods
RNA, Small Interfering administration & dosage
Nanoparticles administration & dosage
Nanoparticles chemistry
Plasmids administration & dosage
DNA administration & dosage
DNA immunology
Mice, Inbred C57BL
Subjects
Details
- Language :
- English
- ISSN :
- 1873-4995
- Volume :
- 369
- Database :
- MEDLINE
- Journal :
- Journal of controlled release : official journal of the Controlled Release Society
- Publication Type :
- Academic Journal
- Accession number :
- 38493950
- Full Text :
- https://doi.org/10.1016/j.jconrel.2024.03.018