Photoresponsive Vesicles Enabling Sequential Release of Nitric Oxide (NO) and Gentamicin for Efficient Biofilm Eradication

Abstract

The development of new antibacterial agents that can efficiently eradicate biofilms is of crucial importance to combat persistent and chronic bacterial infections. Herein, the fabrication of photoresponsive vesicles capable of the sequential release of nitric oxide (NO) and gentamicin sulfate (GS) is reported, which can not only efficiently disperse Pseudomonas aeruginosa (P. aeruginosa) PAO1 biofilm but also kill the planktonic bacteria. Well‐defined amphiphilic diblockcopolymers of poly(ethylene oxide)‐b‐poly(4‐((2‐nitrobenzyl)(nitroso)amino)benzyl methacrylate) (PNO) is first synthesized through atom transfer radical polymerization (ATRP). The PNO diblock copolymer self‐assembled into vesicles in aqueous solution, and a hydrophilic antibiotic of GS is subsequently encapsulated into the aqueous lumens of vesicles. The vesicles undergo visible light‐mediated N‐NO cleavage, releasing NO and disintegrating the vesicles with the release of the GS payload. The sequential release of NO and GS efficiently eradicate P. aeruginosa PAO1 biofilm and kill the liberated bacteria, showing a better antibiofilm effect than that of NO or GS alone.

Photoresponsive Micelles Enabling Codelivery of Nitric Oxide and Formaldehyde for Combinatorial Antibacterial Applications

“…Recently, we have successfully synthesized NO-releasing diblock copolymers based on photoresponsive N -nitrosamine moieties. , These NO-releasing diblock copolymers self-assembled into vesicles in an aqueous solution without premature NO leakage. However, phototriggered NO release was achieved under ultraviolet (UV) or visible light irradiation, showing potential applications in corneal wound healing and biofilm dispersal.…”

“…We found that the micellar nanoparticles were relatively stable in an aqueous solution, and the sizes of micellar nanoparticles showed negligible changes and no macroscopic precipitates were observed within at least one week, as monitored by DLS (Figure S6). Moreover, our previous results suggested that PNO diblock copolymers had a CMC value of ∼32 mg/L, which self-assembled into vesicular nanoparticles in an aqueous solution …”

“…As such, a plethora of NO-releasing materials have been developed − and their antibacterial performance was systematically evaluated, − revealing a board-spectrum antibacterial activity with a low risk of resistance development. ,,, It should be mentioned that the antibacterial performance of NO is highly concentration-dependent. That is, NO can not only efficiently disperse bacterial biofilms at low concentrations but also kill planktonic bacteria at elevated doses. − Note that the formation of bacterial biofilms invalidated conventional antibiotics, making it rather challenging to treat biofilm-related infections . The unique biofilm dispersal and bacterial killing capacity of NO thus made it a promising candidate for new antibiotics …”

Recent Developments in Nitric Oxide Donors and Delivery for Antimicrobial and Anti-Biofilm Applications

“…Nguyen et al attached a NO-releasing moiety to gentamicin within a polymeric nanoparticle for simultaneous release of both compounds and observed synergistic effects against P. aeruginosa [54]. In addition, Duan et al designed photoreceptive of NO-releasing amphiphiles that can self-assemble into vesicles and incorporate the water-soluble gentamicin antibiotic within the vesicle, enabling sequential release of NO and gentamicin upon photoirradiation [55].…”

Photo-Responsive Micelles with Controllable and Co-Release of Carbon Monoxide, Formaldehyde and Doxorubicin

“…Simultaneous release of NO and DOX or gentamicin has also been realized by rational molecular design. [29,30] The outcomes indicate an increased antimicrobial property and synergistic effects on antitumor by controlled and simultaneous release of signaling molecules and antibiotics or antitumor agents. However, the combined donor for CO and FA has never been attempted.…”