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

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. A 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, because 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 triblock 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 antitumor activity.

• Authors: Nak Won Kim, Sun-Young Kim, Jung Eun Lee, Yue Yin, Jong Han Lee, Su Yeon Lim, E Seul Kim, Huu Thuy Trang Duong, Hong Kee Kim, Sohyun Kim, Jung-Eun Kim, Doo Sung Lee, Jaeyoon Kim, Min Sang Lee, Yong Taik Lim, Ji Hoon Jeong
• Journal: ACS nano (ACS Nano) Vol. 12 Issue 10 Pg. 9702-9713 (10 23 2018) ISSN: 1936-086X [Electronic] United States
• PMID: 30141896 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adjuvants, Immunologic
• Antigens, Neoplasm
• Cancer Vaccines
• Imidazoles
• Micelles
• Polymers
• Surface-Active Agents
• resiquimod

Topics

• Adjuvants, Immunologic (administration & dosage, therapeutic use)
• Animals
• Antigen-Presenting Cells (chemistry, immunology)
• Antigens, Neoplasm (administration & dosage, immunology)
• Cancer Vaccines (chemistry, immunology)
• Drug Delivery Systems
• Female
• HCT116 Cells
• Humans
• Imidazoles (administration & dosage, pharmacology)
• Lymph Nodes (drug effects, immunology)
• Mice
• Mice, Inbred C57BL
• Micelles
• Nanoparticles (chemistry)
• Needles
• Neoplasms, Experimental (immunology, pathology, therapy)
• Polymers (chemistry)
• RAW 264.7 Cells
• Surface-Active Agents (chemistry)
• Vaccination