Bacterial infection, hypoxia, and inflammatory stress responses are the key obstacles that delay the healing of diabetic ulcers. Herein, DMSNs-Pt-LOX@Nisin (DPLN) nanomotors that exhibits cascade propulsion and can specifically target methicillin-resistant Staphylococcus aureus (MRSA) is developed. The DPLN can facilitate the conversion of the abundant lactic acid existed in diabetic wounds, resulting in the generation of hydrogen peroxide (H 2 O 2 ). Meanwhile, the unilateral Pt nanodendrites (Pt DNs) catalyze H 2 O 2 to produce O 2 , driving the nanomotors to rapidly penetrate into the biofilm. Moreover, by loading Nisin, which can bind to lipid II of Gram-positive bacteria, the nanomotors can target MRSA through a self-driven process. Both in vitro and in vivo experiments demonstrate that the nanomotors can eradicate MRSA biofilms. Furthermore, animal studies show that DPLN are able to expedite the process of wound healing in diabetic mice through the eradication of biofilms, facilitation of angiogenesis, and mitigation of inflammation. These novel nanomotors combining cascade propulsion and MRSA targeting represent an encouraging and potentially effective approach in diabetic ulcer treatment.
Background : Biofilm infection caused by multidrug-resistant bacteria is difficult to eradicate by conventional therapies. Photodynamic therapy (PDT) is an effective antibacterial method for fighting against biofilm infection. However, the blocked photosensitizers outside of biofilm greatly limit the efficacy of PDT. Methods : Herein, a novel acid-responsive superporogen and photosensitizer (SiO 2 -P Ce6-IL ) was developed. Because of the protonation of the photosensitizer and the high binding energy of the polyionic liquid, SiO 2 -P Ce6-IL changed to positive SiO 2 -P IL + in an acidic microenvironment of biofilm infection. SiO 2 -P IL + could combine with negatively charged extracellular polymeric substances (EPS) and create holes to remove the biofilm barrier. To strengthen the interaction between SiO 2 -P IL + and EPS, SiO 2 -P IL + of high charge density was prepared by grafting the high-density initiation site of ATRP onto the surface of the SiO 2 base. Results : Due to the rapid protonation rate of COO - and the strong binding energy of SiO 2 -P IL + with EPS, SiO 2 -P Ce6-IL could release 90% of Ce6 in 10 s. With the stronger electrostatic and hydrophobic interaction of SiO 2 -P IL + with EPS, the surface potential, hydrophobicity, adhesion and mechanical strength of biofilm were changed, and holes in the biofilm were created in 10 min. Combining with the release of photosensitizers and the porous structure of the biofilm, Ce6 was efficiently concentrated in the biofilm. The in vitro and in vivo antibacterial experiments proved that SiO 2 -P Ce6-IL dramatically improved the PDT efficacy against MRSA biofilm infection. Conclusion : These findings suggest that SiO 2 -P Ce6-IL could rapidly increase the concentration of photosensitizer in biofilm and it is an effective therapy for combating biofilm infection.
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