Polyphenol-based nanoparticles enhancing doxycycline efficacy for acne therapy.

Acne is an inflammatory dermatological disorder largely caused by Cutibacterium acnes (C. acnes), which primarily affects the face, neck, chest, and back, leading to skin impairment. This condition is often associated with post-inflammatory erythema, hyperpigmentation, and scarring, as well as psychosocial and emotional distress. Based on the major pathological characteristics of acne with microbiome colonization, and multiple immune responses, we selected doxycycline, a common clinically used antibiotic and anti-inflammatory drug, and epigallocatechin gallate (EGCG), a polyphenol, to construct topically applicable nanoparticles (NPs). The resulting doxycycline-EGCG (DE) NPs significantly reduced the proportion of dead cells in C. acnes-induced HaCaT cells and demonstrated excellent anti-inflammatory effects through inhibition of NF-κB and STAT3 pathways compared to doxycycline alone. Moreover, the DE NPs exhibited better antibacterial efficacy against C. acnes along with improved antioxidant capacity than doxycycline. In an acne-like mouse model, the DE NPs also effectively suppressed skin inflammation and reduced inflammatory cytokine expression. Overall, this work presents a co-assembly strategy driven by covalent and non-covalent interactions, affording polyphenol-based doxycycline NPs with potent anti-inflammatory, antioxidant and antibacterial properties, and offering new opportunities for safe and effective acne local therapy.