Acne vulgaris, generally resulted from overgrowth of Propionibacterium acnes (P. acnes), is one of the most difficult-to-treat facial dermatoses and more than 90% of adolescents experienced the disease worldwide. Because the innate non-lymphoid immune system cannot effectively eliminate excessive P. acnes from the skin surface, so far the therapy of acne vulgaris is still mainly dependent on antibiotic treatment. However, long-term or overdose of antibiotics may initiate microbial drug resistance and/or generate unexpected side effects that seriously hamper the use of antibiotics in the clinic. To overcome the aforementioned challenges, the novel rifampicin (RIF)-indocyanine green (ICG)-loaded perfluorocarbon (PFC) nanodroplets (RIPNDs) that may offer combined photo-, chemo-, and probiotic efficacies to P. acnes eradication were developed in this study. The RIPND was first characterized as a sphere-like nanoparticle with surface charge of −20.9 ± 2.40 mV and size of 240.7 ± 6.73 nm, in which the encapsulation efficiencies of RIF and ICG were 54.0 ± 10.5% and 95.0 ± 4.84%, respectively. In comparison to the freely dissolved ICG, the RIPNDs conferred an enhanced thermal stability to the entrapped ICG, and were able to provide a comparable hyperthermia effect and markedly increased production of singlet oxygen under near infrared (NIR; 808 nm, 6 W/cm2) exposure. Furthermore, the RIPNDs were able to induce fermentation of S. epidermidis but not P. acnes, indicating that the RIPNDs may serve as a selective fermentation initiator for the target probiotics. Based on the microbial population index analyses, P. acnes with 1 × 106 cells/mL can be completely eradicated by 12-h co-culture with S. epidermidis fermentation products followed by treatment of RIPNDs (≥20-μM ICG/3.8-μM RIF) + NIR for 5 min, whereby the resulted microbial mortality was even higher than that caused by using 16-fold enhanced amount of loaded RIF alone. Overall these efforts show that the RIPNDs were able to provide improved ICG stability, selective fermentability to S. epidermidis, and enhanced antimicrobial efficacy compared to equal dosage of free RIF and/or ICG, indicating that the developed nanodroplets are highly potential for use in the clinical anti-P. acne treatment with reduced chemotoxicity.

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Acne vulgaris is one of the most prevalent dermatological diseases among adolescents and is often associated with overgrowth of Cutibacterium acnes (C. acnes) in the pilosebaceous units. In this study, we aimed to develop novel rifampicin (RIF) and indocyanine green (ICG) co-loaded perfluorocarbon nanodroplets named RIPNDs which can simultaneously provide photo-, chemo-, and probiotic-antimicrobility, and explore their efficacy in treatment of C. acnes in vitro and in vivo. The RIPNDs were first characterized as being spherical in shape, with a size of 238.6 ± 7.51 nm and surface charge of −22.3 ± 3.5 mV. Then, the optimal dosages of Staphylococcus epidermidis–produced fermentation product medium (FPM) and RIPND were determined as 25% (v/v) and [RIF]/[ICG] = 3.8/20 μM, respectively, based on the analyses of inhibition zone and cytotoxicity in vitro. Through the in vivo study using C. acnes–inoculated mice, our data showed that the group treated with FPM followed by RIPNDs + near infrared (NIR) irradiation obtained the least granulocytes/macrophage-inflammatory protein 2 expression level in the epidermis, and showed a significantly lower microbial colony population compared to the groups treated with equal amount of RIF, FPM, RIPNDs, and/or combination of the above ± NIR. These results indicated that the RIPND-mediated photo–chemo–probiotic therapeutics was indeed able to rapidly suppress inflammatory response of the skin and provide a robust antibacterial effect against C. acnes with limited use of antibiotics. Taken altogether, we anticipate that the RIPND is highly potential for use in the clinical treatment of acne vulgaris.