Smart vaccine delivery based on microneedle arrays decorated with ultra-pH-responsive copolymers for cancer immunotherapy

Recent Advances in Polymeric Nanomedicines for Cancer Immunotherapy

“…After the MNs are dissolved in the skin within minutes, antigen‐loaded PLGA nanoparticles can be exposed to the skin layers abundant with APCs, facilitating the specific skin DCs targeting with controlled antigen release and distribution which leads to their efficient activation of DCs. Unlike dissolvable MNs encapsulating antigen‐loaded nanoparticles, Duong et al developed a smart DNA vaccine delivery system using MNs assembled with layer‐by‐layer (LbL) coating of pH‐responsive charge convertible copolymer oligo sulfamethazine conjugated poly(β‐amino ester urethane) (OSM‐(PEG‐PAEU)) and negatively charged immunostimulatory adjuvant poly(I:C) ( Figure A) . Following the construction of polyelectrolyte multilayer assembly, the cationic polyplex‐bearing pOVA vaccines were loaded on the outermost anionic layer of MNs.…”

Transcutaneous delivery of DNA/mRNA for cancer therapeutic vaccination

“…Hollow microneedle‐mediated TCI in combination with cationic niosomes/OVA pDNA complexes and PEI/OVA pDNA polyplexes was reported to achieve intradermal delivery and enhanced transfection efficiency simultaneously. Furthermore, Duong et al . proposed a smart OVA pDNA vaccine delivery system in which pDNA/PEI‐derivative polyplexes were laden on solid microneedles assembled with a layer‐by‐layer coating comprising an ultra‐pH‐responsive copolymer and TLR‐3 agonist poly(I:C).…”

“…proposed a smart OVA pDNA vaccine delivery system in which pDNA/PEI‐derivative polyplexes were laden on solid microneedles assembled with a layer‐by‐layer coating comprising an ultra‐pH‐responsive copolymer and TLR‐3 agonist poly(I:C). Upon skin implantation, the copolymer became negatively charged and thus triggered DNA and adjuvant release by electrostatic repulsion, and OVA protein was found to be expressed in DCs and macrophage cells; the synergistic effect of pOVA and adjuvant generated good humoral and cellular immunity . Compared to DNA, the biggest challenge for mRNA immunization is the lability and easy degradation of mRNA.…”

“…Hollow microneedle-mediated TCI in combination with cationic niosomes/ OVA pDNA complexes 70 and PEI/OVA pDNA polyplexes 109 was reported to achieve intradermal delivery and enhanced transfection efficiency simultaneously. Furthermore, Duong et al 110 proposed a smart OVA pDNA vaccine delivery system in which pDNA/PEIderivative polyplexes were laden on solid microneedles assembled with a layer-by-layer coating comprising an ultra-pH-responsive copolymer and TLR-3 agonist poly(I:C). Upon skin implantation, the copolymer became negatively charged and thus triggered DNA and adjuvant release by electrostatic repulsion, and OVA protein was found to be expressed in DCs and macrophage cells; the synergistic effect of pOVA and adjuvant generated good humoral and cellular immunity.…”

“…Upon skin implantation, the copolymer became negatively charged and thus triggered DNA and adjuvant release by electrostatic repulsion, and OVA protein was found to be expressed in DCs and macrophage cells; the synergistic effect of pOVA and adjuvant generated good humoral and cellular immunity. 110 Compared to DNA, the biggest challenge for mRNA immunization is the lability and easy degradation of mRNA. The loading of mRNA on a dissolving microneedle patch (RNApatch) not only avoided the unwanted degradation caused by Rnase, but also improved the shelf life of mRNA.…”