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 (BiO2-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 (Eads = -1.821 eV). Under ultrasound irradiation, the patch demonstrates superior piezo-sonocatalytic activity (≈0.6 V piezoelectric output and d33 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 BiO2-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.