The development of a safe, effective, and accessible human immunodeficiency virus 1 (HIV-1) vaccine remains a global priority, and nanoparticles (NPs) have emerged as a promising platform for vaccine delivery. However, the efficacy of protein-based NP vaccines is often limited by pre-existing immunity against scaffold components. In this study, we developed a novel HIV-1 vaccine platform by converting self-assembling human papillomavirus (HPV) L1 virus-like particles (VLPs) into immune-stealth biomaterials for focused antigen delivery. Encapsulation of VLPs within a silica shell provided both immune shielding and a surface for site-specific antigen conjugation. The resulting L1-SiO2 NPs were covalently functionalized with HIV-1 Env trimers (L1-SiO2-Env) and characterized for their physicochemical properties and immunogenicity. In vivo, the silica coating effectively masked L1-specific B cell epitopes, reduced anti-scaffold IgG responses and enhanced Env-specific antibody production in mice pre-immunized against HPV. This synthetic strategy offers a versatile platform for overcoming scaffold-directed immunity in nanoparticle vaccines.

The design of drug delivery systems (DDS) for efficient and sustained in situ antioxidant treatment is demanded in regenerative medicine applications. DDS, based on nanoparticle-loaded hydrogels, are promising advanced drug delivery platforms to achieve prolonged release and targeted bioactivity. Herein we developed innovative and sustainable injectable hydrogels based on oxidized pectin (PDA) and carbohydrazide-modified gelatin (G-CDH) for the release of curcumin-loaded zein nanoparticles (CurZNPs) for mitigating cell oxidative stress. CurZNPs, produced by nanoprecipitation, exhibited high encapsulation efficiency, sustained curcumin release, and strong antioxidant and anti-inflammatory activities. PDA/G-CDH hydrogels with three different PDA : G-CDH ratios were prepared by double physical and chemical crosslinking, through calcium ions internally released from CaCO3 and Schiff base formation between PDA and G-CDH functional groups, respectively. PDA/G-CDH hydrogels showed rheological tunability, depending on the degree of pectin oxidation (2.5 mol%: PDA_2.5 and 5 mol%: PDA_5). Hydrogels with a balanced aldehyde-to-amine ratio, specifically the PDA_2.5/G-CDH (70 : 30) and PDA_5/G-CDH (50 : 50) formulations, were selected based on their superior stability in physiological conditions, consistent with effective crosslinking. Such compositions also exhibited injectability through shear thinning behaviour, and self-healing by restored mechanical integrity after stress, and supported human fibroblast viability and attachment. CurZNPs-loaded PDA/G-CDH hydrogels showed prolonged curcumin release, antioxidant activity by restoring fibroblast viability after induced oxidative damage, and anti-inflammatory properties with RAW 264.7 macrophages. In conclusion, injectable PDA/G-CDH hydrogels were efficient and biocompatible DDS for antioxidant treatment through controlled CurZNPs release.

Phenylboronic acid (PBA) and its ester derivates (PBE) are considered adaptable building blocks for smart biomaterials, enabling precision in therapeutic and diagnostic applications. Their reversible covalent interactions with cis-diols allow selective recognition of clinically relevant biomarkers including glucose, reactive oxygen species (ROS), and sialic acid (Sia). These properties have been exploited to engineer responsive systems for glucose-triggered insulin and glucagon delivery, ROS-mediated drug release in oxidative microenvironments, and Sia-targeted cancer therapies. Recent advances integrate PBA/PBE chemistries into multi-responsive platforms, closed-loop devices, and biosensors for real-time monitoring, making these materials key enablers of personalized treatment strategies. Here, we review design principles that govern binding specificity, summarize applications across a wide range of therapies, and discuss key challenges such as off-target interactions and physiological stability. Finally, we outline opportunities for clinical translation, positioning PBA/PBE-based materials as promising candidates for next generation precision medicines.