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.

Advanced biomaterials for cancer immunotherapy

“…As a significant research target, microneedles have been used in many aspects, such as the delivery of small molecule and protein drugs and vaccines [242][243][244]. It is an inexpensive and [255] convenient way to use microneedles for various medical applications [245][246][247][248][249]. There are many lymph nodes in the dermis; thus, microneedles achieve direct contact with DCs for antigen uptake and presentation [27].…”

Exploring Essential Issues for Improving Therapeutic Cancer Vaccine Trial Design

“…Virosomes are liposomes containing viral proteins that permit fusion with target cells and deliver adjuvants and/or expression of tumor antigens by the target cells [ 19 ]. Microneedles are promiscuous delivery adjuvants and proteins or genetic material through the skin barrier inducing potent antitumor responses [ 20 , 21 ].…”

Recent Advances in Particulate Adjuvants for Cancer Vaccination

“…There are two main ways for vaccines to reach lymph nodes. One way is to be captured by resident APCs, such as DCs and macrophages, and then homing to the lymph nodes . The other way is to move the vaccine antigen across the extracellular matrix and into the lymphatics to reach the lymph nodes along the lymphatic circulation .…”