poly(D,L-lactide-co-glycolide) nanoparticles as a vaccine delivery platform for TLR7/8 agonist-based cancer vaccine
2019
Drug delivery to target site is critical as it can significantly influence the efficacy of the drug. In the past decades, diverse drug delivery technologies including nano/micro particles, cocrystals, and microneedles have been developed to maximize the therapeutic efficacy, and to minimize the undesired side effects of the therapeutics. Nanoparticles which are sub-micron size drug carriers, have actively investigated for the delivery of antibiotics, nucleic acids, peptide/proteins, and chemotherapeutics. Recently, nanoparticles have gained attention as vaccine delivery platform for the delivery of tumor-associated antigens (TAAs) and/or vaccine adjuvants. Imidazoquinoline-structured toll-like receptor (TLR) 7/8 agonists are potent cytokine inducers that are utilized as cancer vaccine adjuvant to elicit robust T cell response by activating dendritic cells (DCs). Despite its in vitro potency, its clinical translation as cancer vaccine adjuvant is limited due to their cream and gel formulation that narrows their application to topical treatments. Therefore, a formulation that can deliver the TLR7/8 agonist via conventional vaccine injection routes (subcutaneous, intramuscular) can broaden the application of TLR7/8 agonists for cancer immunotherapy. Polymeric nanoparticles fabricated with poly(lactide-co-glicolide) (PLGA) can be an efficient TLR7/8 agonist delivery platform. PLGA is biocompatible polymer and can be prepared in buffered saline, which allows the subcutaneous/intramuscular injection of TLR7/8 agonists. Furthermore, nanoparticulate TLR7/8 delivery can enhance the DC uptake and facilitate lymphatic drainage, both, which can enhance the adjuvanticity of TLR7/8 agonists compared to soluble form. In this review, we introduce PLGA nanoparticles as drug carrier of TLR7/8 agonists for enhanced cancer immunotherapy.
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