Engineered Hydroxyapatite Nanoadjuvants with Controlled Shape and Aspect Ratios Reveal Their Immunomodulatory Potentials.

Hydroxyapatite (HAP) has been formulated as adjuvants in vaccines for human use. However, the optimal properties required for HAP nanoparticles to elicit adjuvanticity and the underlying immunopotentiation mechanisms have not been fully elucidated. Herein, a library of HAP nanorods and nanospheres was synthesized to explore the effect of the particle shape and aspect ratio on the immune responses in vitro and adjuvanticity in vivo. It was demonstrated that long aspect ratio HAP nanorods induced a higher degree of cell membrane depolarization and subsequent uptake, and the internalized particles elicited cathepsin B release and mitochondrial reactive oxygen species generation, which further led to pro-inflammatory responses. Furthermore, the physicochemical property-dependent immunostimulation capacities were correlated with their humoral responses in a murine hepatitis B surface antigen immunization model, with long aspect ratio HAP nanorods inducing higher antigen-specific antibody productions. Importantly, HAP nanorods significantly up-regulated the IFN-γ secretion and CD107α expression on CD8+ T cells in immunized mice. Further mechanistic studies demonstrated that HAP nanorods with defined properties exerted immunomodulatory effects by enhanced antigen persistence and immune cell recruitments. Our study provides a rational design strategy for engineered nanomaterial-based vaccine adjuvants.

Bienzymatic synergism of vanadium oxide nanodots to efficiently eradicate drug-resistant bacteria during wound healing in vivo.

Antibiotic resistance is a common phenomenon observed during treatment with antibacterials. Use of nanozymes, especially those with synergistic enzyme-like activities, as antibacterials could overcome this problem, but their synthesis is limited by their high cost and/or complex production process. Herein, vanadium oxide nanodots (VOxNDs) were prepared via a one-step bottom-up ethanol-thermal method using vanadium trichloride as the precursor. VOxNDs alone possess bienzyme mimics of peroxidase and oxidase. Accordingly, highly efficient antibacterials against drug-resistant bacteria can be obtained through synergistic catalysis; the oxidase-like activity decomposes O2 to generate superoxide anion radical (O2-) and hydroxyl radicals (OH), and the intrinsic peroxidase-like activity can further induce the production of OH from external H2O2. Consequently, H2O2 concentration could decrease up to four magnitude orders with VOxNDs to achieve an antibacterial efficacy similar to that of H2O2 alone. Wound healing in vivo further confirms the high antibacterial efficiency, good biocompatibility, and application potential of the synergistic antibacterial system due to the "nano" structure of VOxNDs. The method of synthesis of nanodot antibacterials described in this paper is inexpensive, and the results of this study reveal the multi-enzymatic synergism of nanozymes.