ACS nano

Extremely limited drug retention and depigmentation represent the greatest barriers against vitiligo treatment advancement. Here, inspired by biological melanosomes, the primary melanin transporter, we developed biomimetic melanosomes to combat reactive oxygen species (ROS)-mediated melanocyte damage and depigmentation. Briefly, methylprednisolone (MPS) and melanin-mimicking polydopamine (PDA) were encapsulated inside lysine-proline-valine (KPV)-modified deformable liposomes (KPV-Lipos). Owing to their phospholipid bilayer flexibility and the specific affinity for melanocortin 1 receptor (MC1R), KPV-Lipos exhibited 1.43-fold greater skin deposition than traditional liposomes. The binding of KPV and its receptor also contributed to activating the cAMP-tyrosinase (TYR) signaling pathway, improving the endogenous melanin content. In addition, PDA mimicked melanosomes as it effectively increased the exogenous melanin content and scavenged ROS. Meanwhile, MPS inhibited inflammatory cytokine secretion, limiting the depigmented area. Ultimately, the biomimetic melanosomes affected the skin color of mice with H 2 O 2 -induced vitiligo. These melanosomes show potential as a universal platform for the self-supply of melanin by self-driven melanin synthesis with exogenous supplementation. Furthermore, this study offers ideas for the production of artificial packed melanosome substitutes for melanocyte-related diseases.

Chondrocyte senescence, synovitis, and decreased level of lubrication play pivotal roles in the pathogenesis of age-related osteoarthritis (AROA). However, there are currently no effective therapeutic interventions capable of altering the progression of OA until it reaches advanced stages, necessitating joint replacement. In this study, lubricious and drug-loaded hydrogel microspheres were designed and fabricated by utilizing microfluidic technology for radical polymerization of chondroitin sulfate methacrylate and incorporating nicotinamide adenine dinucleotide (NAD)-loaded liposomes modified with lactoferrin that are positively charged. Mechanical, tribological, and drug release analyses demonstrated enhanced lubrication properties and an extended drug dissemination time for the NAD@NPs@HM microspheres. In vitro assays unveiled the ability of NAD@NPs@HM to counteract chondrocyte senescence. RNA sequencing analysis, untargeted metabolomics analysis, and in vitro experiments on macrophages revealed that NAD@NPs@HM can regulate the metabolic reprogramming of synovial macrophages, promoting their repolarization from the M1 to M2 phenotype, thereby alleviating synovitis. Intra-articular injection of NAD@NPs@HM in aged mice reduced the mechanisms associated with AROA. These results suggest that NAD@NPs@HM may provide extended drug release, improved joint lubrication leading to better gait, and attenuation of AROA pathogenic processes, indicating its potential as a therapeutic approach for AROA.