Near-Infrared Light-Triggered Synergistic Phototherapy for Antimicrobial Therapy

Abstract

Phototherapy has great advantages in combating bacterial infection, in particular, those therapies mediated by near-infrared light. To advance phototherapy for bacterial infections, a positively charged conjugated polymer (termed PTDBD) with near-infrared light-triggered activity is employed for antimicrobial therapy in this paper. The quaternary ammonium groups in side chains of PTDBD can benefit from the interaction between the polymer and negatively charged membrane of bacteria, and such a structure can also induce the aggregation of bacteria to improve local antibacterial efficiency. Upon single near-infrared light irradiation, simultaneous reactive oxygen species (ROS) and heat generated by the polymer PTDBD can effectively kill bacteria at low treatment concentration (40 μg·mL–1) and low light density (1.0 W·cm–2) toward both Gram-positive bacteria (Staphylococcus aureus) and Gram-negative bacteria (ampicillin-resistant Escherichia coli TOP 10). For fungi (Candida albicans), a higher treatment concentration of PTDBD is needed to kill at the same light density. Finally, the dual phototherapy is also employed to treat the bacteria-infected wound of mice with no tissue damage observed. The integration of positive charges, ROS, and heat provides a highly efficient and broad spectrum antimicrobial strategy for further treatment of bacterial infections in vivo.

Light‐Activated Conjugated Polymers for Antibacterial Photodynamic and Photothermal Therapy

“…[ 76,77 ] Since then, their biomedical application has greatly expanded [ 63 ] as conjugated polymer–based materials have excelled as bioimaging probes, [ 16 ] theranostic agents for cancer treatments, [ 57,78,79 ] drug delivery systems, [ 74,80 ] and light‐responsive antimicrobial agents. [ 9,17,18,21–26,81–84 ] The emerging interest in these promising organic materials is evidenced by the efforts put into the preparation of biodegradable conjugated polymers. [ 85,86 ]…”

“…[ 18–20 ] In fact, conjugated polymers with a sequence of electron‐donating and electron‐accepting units (donor–acceptor structures) have shown enhanced performance as aPDT and aPTT agents. [ 24,54,81,95 ] In this context, conjugated polymers with the same backbone structure but functionalized with electron‐donating and withdrawing groups outperformed the ROS generation and antimicrobial activity of their counterpart functionalized with two strong electron‐accepting groups. [ 20 ] In addition, conjugated polymers with increasing electron‐withdrawing benzothiadiazole (BT) units presented a decrease in their fluorescence emission, augmented singlet oxygen ( 1 O 2 ) generation, and greater antibacterial activity under visible light irradiation.…”

“…[ 95 ] In effect, the benzothiazole‐containing conjugated polymer generated ROS and heat under laser illumination, which combined were responsible for the antimicrobial activity (Figure 4). [ 81 ] Moreover, by substituting phenylenene by BT in fluorene‐ co ‐phenylenene‐based conjugated polymers [ 18 ] and increasing the length of side chains [ 19 ] the authors observed augmented ROS generation and enhanced antimicrobial effect. Also, cationic poly(fluorene‐ co ‐phenyl‐eneethynylene) (PFE) derivatives showed enhanced ROS production and antimicrobial activity compared to a conjugated polymer based on poly(fluorinephenylene) (PFP).…”

“…[ 9,23,58,96 ] Although the association of different conjugated polymers with complementary optical properties has generated nanoparticles that can achieve aPTT and aPDT against bacteria, [ 23,96 ] a single conjugated polymer with donor–acceptor structure based on thiophene (electron‐rich) and benzothiadiazole and diketopyrrolopyrrole (electron‐deficient) (referred to as PTDBD) was able to generate sufficient ROS and heat to inactivate bacteria through both mechanisms while requiring only one light source (808 nm laser) (Figure 4). [ 81 ]…”

“…Conjugated polymers with absorption in the NIR range have been explored for antibacterial photoresponsive treatments due to the lower light scattering and higher penetration depth of NIR light in tissues. [ 9,23,27,81 ] Another approach to improve their applicability is functionalization with cationic groups to improve the interaction with the heavily negative charged surface of bacteria. [ 17,18,22,24,26,81–84 ] Different conjugated polymers functionalized with quaternary ammonium groups showed cytotoxicity against bacteria in the dark and the bactericidal activity was greatly enhanced following light exposure.…”