Immune Cells Activating Biotin-Decorated PLGA Protein Carrier

Abstract

Nanoparticle formulations have long been proposed as subunit vaccine carriers owing to their ability to entrap proteins and codeliver adjuvants. Poly(lactic-co-glycolic acid) (PLGA) remains one of the most studied polymers for controlled release and nanoparticle drug delivery, and numerous studies exist proposing PLGA particles as subunit vaccine carriers. In this work we report using PLGA nanoparticles modified with biotin (bNPs) to deliver proteins via adsorption and stimulate professional antigen-presenting cells (APCs). We present evidence showing bNPs are capable of retaining proteins through the biotin−avidin interaction. Surface accessible biotin bound both biotinylated catalase (bCAT) through avidin and streptavidin horseradish peroxidase (HRP). Analysis of the HRP found that activity on the bNPs was preserved once captured on the surface of bNP. Further, bNPs were found to have self-adjuvant properties, evidenced by bNP induced IL-1β, IL-18, and IL-12 production in vitro in APCs, thereby licensing the cells to generate Th1-type helper T cell responses. Cytokine production was reduced in avidin precoated bNPs (but not with other proteins), suggesting that the proinflammatory response is due in part to exposed biotin on the surface of bNPs. bNPs injected subcutaneously were localized to draining lymph nodes detectable after 28 days and were internalized by bronchoalveolar lavage dendritic cells and macrophages in mice in a dose-dependent manner when delivered intranasally. Taken together, these data provide evidence that bNPs should be explored further as potential adjuvanting carriers for subunit vaccines.

In vitro anti-trypanosomal activity of 3-(aryl)-6-piperazin1,2,4-triazolo[3,4-a]phthalazines-loaded ultrathin polymeric particles: effect of polymer type and particle size

“…NPs consisting of a drug-loaded polylactic- co -glycolic acid (PLGA) core and wrapped with acid-triggered membrane peptide have shown facilitated internalization into cells within the acidic microenvironment where intracellular conditions degrade the NPs, thereby releasing the chemotherapeutic cargo. 14–21…”

“…NPs consisting of a drug-loaded polylactic-co-glycolic acid (PLGA) core and wrapped with acid-triggered membrane peptide have shown facilitated internalization into cells within the acidic microenvironment where intracellular conditions degrade the NPs, thereby releasing the chemotherapeutic cargo. [14][15][16][17][18][19][20][21] Within the DDSs, those based on polymeric micro-and nanoparticles are ideal for the design of DDSs because it is possible to reach the nano-dimension, which allows for access to small regions of the parasite membrane. 9,10 Among the polymeric matrices, biodegradable and biocompatible PLGA, poly-(D,L-lactic acid) (PLA) and poly-caprolactone (PCL) nanoparticles (NPs) are commonly used for the preparation of NPsloaded drugs.…”

“…In particular, the PLGA-based nanoparticle systems, beyond its function as a drug carrier, have demonstrated the ability to induce humoral and cell-mediated specific immune responses via activation of dendritic cells in animals models. [14][15][16][17][18][19][20][21] Thus, they are a convenient polymeric matrix for the design of antitrypanosomal agents because it is well documented that these parasites are sensitive to the immunological host's effectors.…”