Enhanced Cancer Vaccination by In Situ Nanomicelle-Generating Dissolving Microneedles.

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Enhanced Cancer Vaccination by In Situ Nanomicelle-Generating Dissolving Microneedles.

ACS Nano. 2018 Aug 24;:

Authors: Kim NW, Kim SY, Lee JE, Yin Y, Lee JH, Lim SY, Kim ES, Duong HTT, Kim HK, Kim S, Kim JE, Lee DS, Kim J, Lee MS, Lim YT, Jeong JH

Abstract
Efficient delivery of tumor antigens and immunostimulatory adjuvants into lymph nodes is crucial for the maturation and activation of antigen-presenting cells (APCs), which subsequently induce adaptive antitumor immunity. Dissolving microneedle (MN) has been considered as an attractive method for transcutaneous immunization due to its superior ability to deliver vaccines through the stratum corneum in a minimally invasive manner. However, since dissolving MNs are mostly prepared using water-soluble sugars or polymers for their rapid dissolution in intradermal fluid after administration, they are often difficult to formulate with poorly water-soluble vaccine components. Here, we develop amphiphilic tri-block copolymer-based dissolving MNs in situ that generate nanomicelles (NMCs) upon their dissolution after cutaneous application, which facilitate the efficient encapsulation of poorly water-soluble toll-like receptor 7/8 agonist (R848) and the delivery of hydrophilic antigens. The sizes of NMCs range from 30 to 40 nm, which is suitable for the efficient delivery of R848 and antigens to lymph nodes and promotion of cellular uptake by APCs, minimizing systemic exposure of the R848. Application of MNs containing tumor model antigen (OVA) and R848 to the skin of EG7-OVA tumor-bearing mice induced a significant level of antigen-specific humoral and cellular immunity, resulting in significant anti-tumor activity.

PMID: 30141896 [PubMed - as supplied by publisher]

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