Curcumin-Adapted Nano-Composites within Dissolvable Microneedles for Precision-Tuned Piezo-Sono-Thermal Antibiotic-Free Acne Therapy

The rational design of bioactive molecules to precisely engineer the energy-conversion interfaces represents an unexplored frontier in advanced therapeutics. Herein, we report a curcumin (Cur)-adapted nano-composites (BiO 2-X /Cur), integrated into a dissolvable microneedles (MNs) patch, for synergistic piezo-sono-thermal therapy against drug-resistant skin infections. The natural compound Cur is engineered not merely as an anti-inflammatory agent but as a critical molecular adapter that precisely tunes the interfacial charge dynamics and energy landscape at the composites interface, which extends carrier lifetime to 0.63 ns and significantly enhances oxygen adsorption capacity ( E ads = -1.821 eV). Under ultrasound irradiation, the patch demonstrates superior piezo-sonocatalytic activity (≈0.6 V piezoelectric output and d 33 value of −2.9 × 10 −12 C/N) to release reactive oxygen species and simultaneously delivers a substantial sono-thermal effect (ΔT > 20 °C). The dissolvable MNs platform ensures precise and painless intradermal delivery of BiO 2-X /Cur, enabling in vitro and in vivo near-complete eradication (>99.97%) of Propionibacterium acnes and methicillin-resistant Staphylococcus aureus , downregulating pro-inflammatory cytokines (IL-6, TNF-α, HIF-1α) while upregulating reparative markers (IL-10, Nrf2). This work establishes an emerging paradigm of using natural molecules as precision adapters for engineering high-performance composites, offering an intelligent and versatile platform for treating complex infectious diseases.