A multifunctional platform with single-NIR-laser-triggered photothermal and NO release for synergistic therapy against multidrug-resistant Gram-negative bacteria and their biofilms

Abstract

Background: Infectious diseases caused by multidrug-resistant (MDR) bacteria, especially MDR Gram-negative strains, have become a global public health challenge. Multifunctional nanomaterials for controlling MDR bacterial infections via eradication of planktonic bacteria and their biofilms are of great interest. Results: In this study, we developed a multifunctional platform (TG-NO-B) with single NIR laser-triggered PTT and NO release for synergistic therapy against MDR Gram-negative bacteria and their biofilms. When located at the infected sites, TG-NO-B was able to selectively bind to the surfaces of Gram-negative bacterial cells and their biofilm matrix through covalent coupling between the BA groups of TG-NO-B and the bacterial LPS units, which could greatly improve the antibacterial efficiency, and reduce side damages to ambient normal tissues. Upon single NIR laser irradiation, TG-NO-B could generate hyperthermia and simultaneously release NO, which would synergistically disrupt bacterial cell membrane, further cause leakage and damage of intracellular components, and finally induce bacteria death. On one hand, the combination of NO and PTT could largely improve the antibacterial efficiency. On the other hand, the bacterial cell membrane damage could improve the permeability and sensitivity to heat, decrease the photothermal temperature and avoid damages caused by high temperature. Moreover, TG-NO-B could be effectively utilized for synergistic therapy against the in vivo infections of MDR Gram-negative bacteria and their biofilms and accelerate wound healing as well as exhibit excellent biocompatibility both in vitro and in vivo. Conclusions: Our study demonstrates that TG-NO-B can be considered as a promising alternative for treating infections caused by MDR Gram-negative bacteria and their biofilms.

Advances and Potentials of Polydopamine Nanosystem in Photothermal-Based Antibacterial Infection Therapies

“…DNase I has also been shown to have the ability to destroy bacterial cell membranes; thus, DNase-CO@MPDA NPs also indicated a powerful killing effect on MRSA by combining the antibacterial effects of DNase, CO, and PDA-mediated PTT ( Yuan et al, 2021 ). Similar functional nanoplatforms could also be used for the treatment of Gram-negative bacteria with multiple-drug resistance ( Zhao et al, 2020 ). This shows that the PDA nanosystem has great potential to explore new antibacterial modes to reduce the occurrence of multiple-drug-resistant bacteria.…”

“…Inspired by the PTT-based anticancer strategy, PTT has also been explored in different bacterial systems to explore their potential for antibacterial treatments ( Xu M. et al, 2020 ; Zhao et al, 2020 ). The light-transferred heat could not only directly destroy bacterial structure and functions ( Yuwen et al, 2018 ) but also introduce more potent antibacterial immunity against intracellular bacterial infections ( Yan M. et al, 2019 ).…”

Near-Infrared Light Brightens Bacterial Disinfection: Recent Progress and Perspectives

“…Gas therapy has been utilized as an alternative non-invasive treatment for combating bacterial infections lately. 169,170 Gaseous-signaling molecules (GSMs), including hydrogen (H 2 ), nitric oxide (NO), sulfur dioxide (SO 2 ), hydrogen sulfide (H 2 S), and carbon monoxide (CO), not only cause negligible side effects to living organisms with high antibacterial capacity but also act as endogenous signal transmitters to induce various biochemical changes in the organism. 171 Nitric oxide, as an important molecule involved in the immune responses and wound healing process, has been widely chosen to be cooperative with antibacterial photothermal treatment.…”

Nitric oxide-propelled nanomotors for bacterial biofilm elimination and endotoxin removal to treat infected burn wounds

“…Although high temperatures destroy biofilms, they inevitably damage the surrounding normal tissues. 10 ROS generated via chemodynamic and photodynamic reactions destroy bacterial walls, membranes and other essential substances ( e.g. DNA and proteins).…”