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 H2O2-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.