Bio-inspired suction cup microneedle loaded fusion membrane targeting nano-drug delivery system treat androgenetic alopecia

Androgenetic alopecia (AGA) involves androgen-driven dermal papilla cell (DPC) dysfunction compounded by oxidative stress and inflammation. We engineered a leech-inspired suction-cup microneedle platform SC/MN@memPDA to deliver metformin precisely to the dermal papilla. The system integrates 300-µm short microneedles with suction-assisted negative pressure to increase insertion depth, mesoporous polydopamine nanoparticles (MPDA) for high-capacity, H₂O₂-responsive MET release, and a fusion membrane cloak derived from M2 marcophages and DPCs for inflammation targeting and dermal papilla niche homing. This system shows anti-inflammation and anti-oxidant stress damage effect both in vitro and in vivo, demonstrates sufficient delivery depth and precise delivery site, and also reveals a positive regulatory effect on hair growth. Collectively, SC/MN@memPDA provides minimally painful, follicle-targeted delivery and reactivating regenerative signaling effect, offering a promising therapeutic strategy for AGA. Graphic abstract of SC/MN@memPDA for AGA treatment. A bioinspired suction-cup microneedle system (SC/MN@memPDA) combinesmesoporous polydopamine nanoparticles with dual cell-membrane coatings for follicle-targeted delivery, alleviating oxidative stress andinflammation while reactivating regenerative signaling to promote hair follicle regeneration in an AGA-like model. TMB: 1,3,5-Trimethylbenzene; F127: Pluronic F127; MET: Metformin; DPCs: Dermal papilla cells; memPDA: Mesoporous polydopamine nanoparticlescoated with dual membranes (dermal papilla cell membrane and M2 macrophage membrane); SC: Suction cup; MN: Microneedle; HF: Hairfollicle