Photonic Crystal-Enhanced Photodynamic Antibacterial Therapy

Photodynamic antibacterial therapy(PDAT)is a kind of rejuvenating strategy that combats bacterial infection due to its admirable characteristics of noninvasiveness and broad-spectrum antibacterial capability.However,the efficiency of PDAT can be greatly hindered by limited light irradiation.Herein,we propose an enhanced PDAT by employing photonic composite films(PCFs)via slow photon and multiple scattering effects.The PCFs are obtained by UV light-initiated polymerization of poly(ethylene glycol)phenyl ether acrylate with a self-assembled SiO_(2)colloidal particle array,followed by the deposition of photosensitizers(PSs).The PCFs can prompt the PSs with matched absorption,which are deposited on their surface,to sufficiently utilize the incident light and generate more reactive oxygen species based on the slow photon phenomenon of photonic crystals and multiple scattering effects of the SiO_(2)colloidal particles.This finding demonstrates the great potential and significance of PCFs in the field of PDAT,which may reduce the requirements of excitation equipment and avoid damage to normal tissues from exposure to huge light energy.

A new class of nitrobenzoic acid-based AIE photosensitizers for highly efficient photodynamic antibacterial therapy

hotodynamic therapy(PDT)has been drawing more and more attention in the antibacterial field.Traditional photosensitizers(PSs)tend to aggregate in aqueous media,which reduces the generation of reactive oxygen species(ROS)and seriously affects the photodynamic efficacy.Many efforts have been made to prevent aggregation of traditional PSs.By contrast,aggregation-induced emission PSs(AIE-PSs)take advantage of aggregation to boost ROS generation and fluorescence intensity.However,the efficacies of the reported antibacterial AIE-PSs are poor.Herein,we report a new class of highly effective antibacterial AIE-PSs based on nitrobenzoic acid structure.TTVBA,a negatively charged AIE-PS,can not only selectively kill spherical bacteria(Staphylococcus aureus(S.aureus))rather than rod-shaped bacteria(Escherichia coli(E.coli)),but also be easily extended to several AIE-PSs(TTVBP1–3)with positive charges and broad-spectrum antibacterial activity.We demonstrate that TTVBP2 can kill3.0 log_(10)of S.aureus at very low concentration(125 nmol L^(-1)),TTVBP3 can kill 4.7 log_(10)of Staphylococcus epidermidis(S.epidermidis)at a concentration of 1μmol L^(-1)and 3.8 log_(10)of E.coli at 5μmol L^(-1),thus enabling them among the most effective antibacterial AIE-PSs reported so far.Meanwhile,these AIE-PSs exhibit excellent wash-free imaging ability for bacteria by simple mixing with bacteria.We thus envision that TTVBA,a nitrobenzoic acid-based extendable AIE-PS,provides a new route for the design of AIE-PSs in antibacterial treatment.

Meso-substituted cationic 3-and 4-N-Pyridylporphyrins and their Zn(II)derivatives for antibacterial photodynamic therapy

Photodynamic inactivation of microorganisms known as antibacterial photodynamic therapy(APDT)is one of the most promising and innovative approaches for the destruction of pathogenic microorganisms.Among the photosensitizers(PSs),compounds based on cationic porphyrins/metalloporphyrins are most successfully used to inactivate microorganisms.Series of meso-substituted cationic pyridylporphyrins and metalloporphyrins with various peripheral groups in the third and fourth positions of the pyrrole ring have been synthesized in Armenia.The aim of this work was to determine and test the most e®ective cationic porphyrins and metalloporphyrins with high photoactivity against Gram negative and Gram positive microorganisms.It was shown that the synthesized cationic pyridylporphyrins/metalloporphyrins exhibit a high degree of phototoxicity towards both types of bacteria,including the methicillinresistant S.aureus strain.Zinc complexes of porphyrins are more phototoxic than metal-free porphyrin analogs.The e®ectiveness of these Zn–metalloporphyrins on bacteria is consistent with the level of singlet oxygen generation.It was found that the high antibacterial activity of the studied cationic porphyrins/metalloporphyrins depends on four factors:the presence in the porphyrin macrocycle of a positive charge(+4),a central metal atom(Zn2þÞand hydrophobic peripheral functional groups as well as high values of quantum yields of singlet oxygen.The results indicate that meso-substituted cationic pyridylporphyrins/metalloporphyrins cannd wider application in photoinactivation of bacteria than anionic or neutral PSs usually used in APDT.

Cationic Conjugated Oligomers for Efficient and Rapid Antibacterial Photodynamic Therapy via Both Type Ⅰ and Type Ⅱ Pathways

Recently,photodynamic therapy(PDT)has attracted wide attention due to its less susceptibility to drug resistance,broad-spectrum biocidal activity and biosafety in normal tissues.However,the traditional photosensitizers(Ps)face the disadvantage of poor therapeutic efficacy due to the requirement of an aerobic environment to generate ^(1)O_(2) through Type Ⅱ pathway.Herein,we designed and synthesized a novel cationic conjugated oligomer oligo(phenylene vinylene)(OPV)and studied its antibacterial photodynamic activity against both Gram-negative Escherichia coli(E.coli)and Gram-positive bacteria methicillin-resistant Staphylococcus aureus(MRSA).Importantly,the OpV can rapidly produce reactive oxygen species(ROs)through double pathways,Type Ⅰ and Ⅱ mechanism under white light irradiation,and efficiently kill E.coli and MRSA at a nanomolar level.The dual type photosensitizing capability makes OPV promising for enhanced PDT to treat pathogens and tumors in complex environments.

Photodynamic eradication of intratumoral microbiota with bacteria-targeted micelles overcomes gemcitabine resistance of pancreatic cancer

Increasing evidence suggests that intratumoral microbiota plays a pivotal role in tumor progression,immunosurveillance,metastasis,and chemosensitivity.Particularly,in pancreatic ductal adenocarcinoma,tumor-resident Gammaproteobacteria could transform the chemotherapeutic drug gemcitabine(Gem)into its inactive form,thus rendering chemotherapy ineffective.Herein,a strategy for selectively eradicating intratumoral bacteria was described for overcoming Gem resistance in a pancreatic cancer animal model.An antimicrobial peptide was linked with photosensitizer through a poly(ethylene glycol)chain,which can self-assemble into micelles with a diameter of∼20 nm.The micelles could efficiently kill bacteria under light irradiation by inducing membrane depolarization,thereby inhibiting Gem metabolism.In a bacteria-resident pancreatic cancer animal model,the selective photodynamic eradication of intratumoral bacteria was demonstrated to efficiently reverse Gem resistance.This research highlights antibacterial photodynamic therapy as a promising adjuvant strategy for cancer therapy by modulating intratumoral microbiota.

Recent advances in engineered polymeric materials for efficient photodynamic inactivation of bacterial pathogens

Nowadays,infectious diseases persist as a global crisis by causing significant destruction to public health and the economic stability of countries worldwide.Especially bacterial infections remain a most severe concern due to the prevalence and emergence of multi-drug resistance(MDR)and limitations with existing therapeutic options.Antibacterial photodynamic therapy(APDT)is a potential therapeutic modality that involves the systematic administration of photosensitizers(PSs),light,and molecular oxygen(O_(2))for coping with bacterial infections.Although the existing porphyrin and non-porphyrin PSs were effective in APDT,the poor solubility,limited efficacy against Gram-negative bacteria,and non-specific distribution hinder their clinical applications.Accordingly,to promote the efficiency of conventional PSs,various polymer-driven modification and function-alization strategies have been adopted to engineer multifunctional hybrid phototherapeutics.This review as-sesses recent advancements and state-of-the-art research in polymer-PSs hybrid materials developed for APDT applications.Further,the key research findings of the following aspects are considered in-depth with constructive discussions:i)PSs-integrated/functionalized polymeric composites through various molecular in-teractions;ii)PSs-deposited coatings on different substrates and devices to eliminate healthcare-associated in-fections;and iii)PSs-embedded films,scaffolds,and hydrogels for regenerative medicine applications.