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Highly potent intradermal vaccination by an array of dissolving microneedle polypeptide cocktail for cancer immunotherapy

Abstract

Despite recent advances in cancer therapy using vaccines, the efficacy of vaccine regimens remains to be improved. Cutaneous transportations of biomolecules, particularly DNA vaccines, have potentially improved therapeutic efficacy and have been found to be appealing approaches in cancer immunotherapy. Nevertheless, the effectiveness of transdermal vaccination is limited by the lack of efficacious immune stimulation. Here, to elicit strong immunogenicity in target cells, we propose an array of dissolving microneedle cocktails for pain-free implantation and triggered release of vaccines and adjuvants at cutaneous tissues. The microneedle cocktails comprising of bioresorbable polypeptide matrix with nanopolyplex, which include cationic amphiphilic conjugates with ovalbumin-expressing plasmid OVA (pOVA) and immunostimulant-polyinosinic:polycytidylic acid (poly(I:C)), were prepared using one-pot synthesis. The cationic nanopolyplex effectively transported pOVA and poly(I:C) into the intracellular compartments of dendritic cells and macrophages. Cutaneous implantation of microneedle cocktails on mice elicits a stronger antigen-specific antibody response than subcutaneous administration of microneedle-free nanopolyplex. Compared with traditional vaccination, dissolving microneedle cocktails enhanced the antibody recall memory after challenge; remarkably, the cocktail-based therapeutic vaccination also resulted in enhanced lung clearance of cancer cells. The dissolving microneedle cocktail therapy based on the triggered release of immunomodulators and adjuvants synergistically augmented the therapeutic effect in B16/OVA melanoma tumors.

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Article information


Submitted
04 Oct 2019
Accepted
06 Jan 2020
First published
08 Jan 2020

J. Mater. Chem. B, 2020, Accepted Manuscript
Article type
Paper

Highly potent intradermal vaccination by an array of dissolving microneedle polypeptide cocktail for cancer immunotherapy

H. T. T. Duong, Y. Yin, T. Thambi, B. S. Kim, J. H. Jeong and D. S. Lee, J. Mater. Chem. B, 2020, Accepted Manuscript , DOI: 10.1039/C9TB02175B

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