Thermoresponsive Liposomes for Photo-Triggered Release of Hypericin Cyclodextrin Inclusion Complex for Efficient Antimicrobial Photodynamic Therapy

Antimicrobial strategies with high efficacy against bacterial infections are urgently needed. The development of effective therapies to control bacterial infections is still a challenge. Herein, near-infrared (NIR)-activated thermosensitive liposomes (TSL) were loaded with the NIR-dye 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide (DiR) and the water-soluble hypericin (Hyp) beta-cyclodextrin inclusion complex (Hyp-beta CD). DiR and Hyp-beta CD loaded thermosensitive liposomes (DH beta CD-TSL) are functionalized for photothermal triggered release and synergistic photodynamic therapy to eliminate the gram-positive Staphylococcus saprophyticus. The dually active liposomes allow the production of heat and singlet oxygen species with the help of DiR and Hyp, respectively. The elevated temperature, generated by the NIR irradiation, irreversibly damages the bacterial membrane, increases the permeation, and melts the liposomes via a phase-transition mechanism, which allows the release of the Hyp-beta CD complex. The photodynamic effect of Hyp-beta CD eradicates the bacterial cells owing to its toxic oxygen species production. DH beta CD-TSL measured the size of 130 nm with an adequate encapsulation efficiency of 81.3% of Hyp-beta CD. They exhibited a phase transition temperature of 42.3 degrees C, while they remained stable at 37 degrees C, and 44% of Hyp-beta CD was released after NIR irradiation (T > 47 degrees C). The bacterial viability dropped significantly after the synergistic treatment (> 4 log(10)), indicating that the NIR-activated TSL have immense therapeutic potential to enhance the antibacterial efficacy. The liposomes showed good biocompatibility, which was confirmed by the cellular viability of mouse fibroblasts (L929).

Automated summary

This study developed near-infrared (NIR)-activated thermosensitive liposomes (TSL) for antibacterial therapy. The liposomes loaded with NIR dye and water-soluble hypericin showed synergistic photothermal and photodynamic effects, effectively eliminating bacterial infections. The results indicate that the NIR-activated TSL have immense therapeutic potential and good biocompatibility.