Transdermal microarrayed electroporation for enhanced cancer immunotherapy based on DNA vaccination.
Proc Natl Acad Sci U S A
; 121(25): e2322264121, 2024 Jun 18.
Article
en En
| MEDLINE
| ID: mdl-38865265
ABSTRACT
Despite the tremendous clinical potential of nucleic acid-based vaccines, their efficacy to induce therapeutic immune response has been limited by the lack of efficient local gene delivery techniques in the human body. In this study, we develop a hydrogel-based organic electronic device (µEPO) for both transdermal delivery of nucleic acids and in vivo microarrayed cell electroporation, which is specifically oriented toward one-step transfection of DNAs in subcutaneous antigen-presenting cells (APCs) for cancer immunotherapy. The µEPO device contains an array of microneedle-shaped electrodes with pre-encapsulated dry DNAs. Upon a pressurized contact with skin tissue, the electrodes are rehydrated, electrically triggered to release DNAs, and then electroporate nearby cells, which can achieve in vivo transfection of more than 50% of the cells in the epidermal and upper dermal layer. As a proof-of-concept, the µEPO technique is employed to facilitate transdermal delivery of neoantigen genes to activate antigen-specific immune response for enhanced cancer immunotherapy based on a DNA vaccination strategy. In an ovalbumin (OVA) cancer vaccine model, we show that high-efficiency transdermal transfection of APCs with OVA-DNAs induces robust cellular and humoral immune responses, including antigen presentation and generation of IFN-γ+ cytotoxic T lymphocytes with a more than 10-fold dose sparing over existing intramuscular injection (IM) approach, and effectively inhibits tumor growth in rodent animals.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Electroporación
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Vacunas de ADN
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Inmunoterapia
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
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Proc. Natl. Acad. Sci. U. S. A
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Proceedings of the national academy of sciences of the United States of America
Año:
2024
Tipo del documento:
Article
País de afiliación:
China