Singlet Oxygen Generation Efficiency Research Articles

Photodynamic inactivation of Staphylococcus aureus in the presence of aggregation-prone photosensitizers based on BODIPY used at submicromolar concentrations.

Two new brominated BODIPYs (1 and 2) bearing amino acid-based chains (l-valine for 1, and dimethyl-l-lysine for 2) were synthesized and characterized. In organic solvents, 1 and 2 were fully soluble and showed the photophysical properties expected for brominated BODIPY dyes, including efficient generation of singlet oxygen (1O2), upon irradiation. In contrast, in aqueous media, both compounds were prone to aggregation and the photo-induced generation of 1O2 was halted. Despite the lack of generation of this reactive species in aqueous media (in cuvette), both 1 and 2 have positive antimicrobial Photodynamic Inactivation (aPDI) effect. The activity against gram-positive Staphylococcus aureus and gram-negative Escherichia coli was determined through the inactivation curves, with a total energy dose of 5.3J/cm2 (white light LED used as an energy source). Compound 2 was highly active against both gram-positive and gram-negative bacteria (3 log CFU/mL reduction was obtained at 0.16μM for S. aureus and 2.5-5.0μM for E. coli), whereas 1 was less effective to kill S. aureus (3 log CFU/mL at 0.32μM) and ineffective for E. coli. The higher efficiency of 2, as compared to 1, to reduce the population of bacteria, can reside in the presence of a protonatable residue in 2, allowing a more effective interaction of this molecule with the cell walls of the microorganisms. In order to explain the lack of reactivity in pure aqueous media (in cuvette) and the contrasting good activity in the presence of bacterial cells it can be hypothesized that upon interaction with the walls of the microorganisms, the aggregated photosensitizers suffer a disaggregation process restoring the ability to generate 1O2, and hence leading to efficient photodynamic activity against these pathogenic microorganisms, in agreement with the similar effect observed recently for porphyrinoid photosensitizers.

J- and H-aggregates of heavy-atom-free Aza-BODIPY dyes with high 1O2 generation efficiency and photodynamic therapy potential

Aggregation of molecules offers a facile way to tune the optical properties of dyes, thus providing a design platform for organic nano-photosensitizers (PSs) with the potential in photodynamic therapy (PDT). However, it is still a great challenge to control the molecular organization of dye monomers to form a specific aggregation to maximize the efficiency of PDT. Herein, we present a novel supramolecular strategy to build nano-PSs from metastable aggregation of heavy-atom-free Aza-BODIPY dyes (BDP-1 and BDP-2) bearing pyridine units, which represented high singlet oxygen (1O2) generation efficiency (up to 0.85–0.89) to overcome the several intrinsic drawbacks of traditional heavy-atom Aza-BODIPY PSs. X-ray crystallographic analysis and theoretical calculations revealed that multiple intermolecular electrostatic interactions triggered the formation of J- and H-aggregates, which transformed excited state properties of the chromophores and promoted the intersystem crossing (ISC) process by reducing singlet-triplet energy gaps (ΔEST) and radiative decay. This study provides insights for clarifying the relationship between molecular structure and aggregates properties by ingenious molecular design and engineering, which should open up new opportunities to construct functional aggregates for PDT.

Engineered Mesoporous Silica-Based Core-Shell Nanoarchitectures for Synergistic Chemo-Photodynamic Therapies.

Combinatorial therapies have garnered enormous interest from researchers in efficiently devastating malignant tumors through synergistic effects. To explore the combinatorial approach, multiple therapeutic agents are typically loaded in the delivery vehicles, controlling their release profiles and executing subsequent therapeutic purposes. Herein, we report the fabrication of core (silica)-shell (mesoporous silica nanoparticles, MSNs) architectures to deliver methylene blue (MB) and cupric doxorubicin (Dox) as model drugs for synergistic photodynamic therapy (PDT), chemotherapy, and chemodynamic therapy (CDT). MB, as the photosensitizer, is initially loaded and stabilized in the silica core for efficient singlet oxygen generation under light irradiation towards PDT. The most outside shell with imidazole silane-modified MSNs is immobilized with a chemotherapeutic agent of Dox molecules through the metal (Copper, Cu)-ligand coordination interactions, achieving the pH-sensitive release and triggering the production of intracellular hydrogen peroxide and subsequent Fenton-like reaction-assisted Cu-catalyzed free radicals for CDT. Further, the designed architectures are systematically characterized using various physicochemical characterization techniques and demonstrate the potent anti-cancer efficacy against skin melanoma. Together our results demonstrated that the MSNs-based core-shell nanoarchitectures have great potential as an effective strategy in synergistically ablating cancer through chemo-, chemodynamic, and photodynamic therapies.

Oxygen‐Generated Hierarchical‐Structured AuNRs@MnO2@SiO2 Nanocarrier for Enhanced NIR‐ and H2O2‐Responsive Mild‐Hyperthermia Photodynamic/Photothermal Combined Tumor Therapy

AbstractTumor hypoxia greatly restricts photodynamic therapy (PDT) efficiency. Photothermal therapy (PTT) implemented at high temperatures induces local skin burning and surrounding tissue damage. Herein, an near‐infrared (NIR)‐ and H2O2‐double responsive heat‐ and O2‐generating core–shell–shell AuNRs@MnO2@SiO2 nanocarrier with Au nanorods (AuNRs) as core and MnO2 as sandwiched nanolayer is developed to realize enhanced photodynamic/photothermal combined tumor therapy at mild‐hyperthermia temperatures. Coating poly‐l‐lysine on AuNRs is capable of preventing AuNRs from aggregation and facilitating the on‐site growth of MnO2. The mesoporous SiO2 nanoshell provides large loading sites for payload indocyanine green (ICG). The MnO2 nanolayer greatly enhances the singlet oxygen (1O2) generation efficiency of ICG both in testing tubes and in cancer cells. Consequently, the O2‐enhanced PDT endows the AuNRs@MnO2@SiO2‐ICG nanoparticles (NPs) dramatically stronger antitumor effect both in vitro and in vivo. Their tumor growth inhibition ratio (67.6%) is significantly higher than that of AuNRs@SiO2‐ICG (28.5%) after one dose intratumor injection and NIR irradiation. Together with their good biosafety, the AuNRs@MnO2@SiO2‐ICG is promisingly translational. The multifunctionality should provide the AuNRs@MnO2@SiO2 NPs a nanocarrier platform for various therapeutic agents to modulate the tumor microenvironment and enhance tumor therapy efficiency.

Mitochondria‐Targeting Boron Dipyrromethene Based Photosensitizers for Enhanced Photodynamic Therapy: Synthesis, Optical Properties, and in vitro Biological Activity

Increasing Investigations show that photosensitizers (PSs) which target mitochondria are useful for enhancing photodynamic therapy (PDT) efficacy. Herein, we carefully designed and synthesized four triphenylphosphonium (TPP)-modified boron dipyrromethene (BDP)-based PSs through Cu(I)-assisted "3+2" cycloaddition reaction. All of them exhibit intense red light absorption with maxima between 659 and 663 nm, considerable fluorescence emission with quantum yields of 0.16-0.23, high singlet oxygen generation efficiency ranging from 0.22 to 0.34, excellent mitochondria-targeting ability, and good biocompatibility. Upon illumination, they induce significant cancer cell death through a mitochondria-related apoptosis pathway. The IC50 values of these BDP dyes against MCF-7 cells were determined to be as low as 0.046-0.113 μM under rather low dosage of light irradiation (1.5 J ⋅ cm-2 ).

Zinc(II), Palladium(II), and Metal-Free Phthalocyanines Bearing Nipagin-Functionalized Substituents against Candida auris and Selected Multidrug-Resistant Microbes.

Due to the rapidly increasing problem of antibiotic resistance in recent years, the use of phthalocyanines as photosensitizers with their superior properties in photodynamic antimicrobial therapy (PACT) applications has become important. In this study, magnesium(II) 1,4,8,11,15,18,22,25-octakis(4-[4-butoxycarbonylphenoxy]butyloxy)phthalocyanine was used in the demetalation reaction in trifluoroacetic acid, and subsequently subjected to metalation reaction in dimethylformamide with zinc(II) acetate and bis(benzonitrile)palladium(II) chloride towards zinc(II) and palladium(II) derivatives. Three phthalocyanines, including a demetalated one as well as two metalated, in the core with zinc(II) and palladium(II) were characterized using 1D and 2D NMR spectroscopy and mass spectrometry. In addition, all macrocycles were subjected to absorption and emission studies as well as photostability tests. In a photochemical study, zinc(II) and palladium(II) phthalocyanine complexes appeared to be efficient singlet oxygen generators. There were noted quantum yields of singlet oxygen generation for zinc(II) phthalocyanine derivative in DMF and DMSO at 0.55 and 0.72, whereas for palladium(II) complex at 0.73 and 0.77, respectively. Liposomal formulations of phthalocyanine derivatives were prepared, and their activity was evaluated against a broad spectrum of antibiotic-resistant microorganisms, such as methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli (ESBL+), Candida albicans resistant to fluconazole, C. auris, and against dermatophytes. Phthalocyanine palladium(II) complex showed the highest bactericidal activity against all antibiotic-resistant microorganisms, including reducing C. auris growth at 3.54 log.

Zwitterionic meso-silica/polypeptide hybrid nanoparticles for efficient azithromycin delivery and photodynamic therapy for synergistic treatment of drug-resistant bacterial infection

The treatment of drug-resistant bacterial infections attributed to the overuse of antibiotics still remains a serious challenge globally. Herein, zwitterionic charge switchable meso-silica/polypeptide hybrid nanoparticles (MSPNs) were prepared for the synergistic chemo-photodynamic therapy in the treatment of drug-resistant bacterial infections. Subsequently, azithromycin (AZT) and methylene blue (MB) were loaded in the MSPNs to form the combined chemo-photodynamic therapeutic nanoparticles (MSPNs-AZT/MB) for the treatment of methicillin-resistant Staphylococcus aureus (MRSA). Remarkably, the as-prepared MSPNs-AZT/MB exhibited a negative surface charge of −5.2 mV at physiological pH while switching into positive surface charge of 24.7 mv in an acidic environment, leading to enhanced binding with bacterial surface. The lipase-triggered AZT release up to 77.9 % was achieved, and the loaded MB demonstrated efficient singlet oxygen (1O2) generation for photodynamic therapy. The in vitro experimental results displayed an excellent antibacterial effect against MRSA in both planktonic and biofilm phenotypes. Additionally, the as-prepared MSPNs-AZT/MB exhibited synergistic and enhanced antibacterial infection effect up to 94 % comparing to monotherapy in a mice model. Considering the above advantages, the as-prepared combined chemo-photodynamic therapeutic nanoparticles showed promising biocompatibility and clinical potential for the efficient therapy of drug-resistant bacteria.

Folic Acid-Modified Cyclodextrin Multivalent Supramolecular Assembly for Photodynamic Therapy.

The construction of supramolecular multivalent assemblies with unique photoluminescence behaviors and biological functions has become a research hot spot recently in the biomaterial field. Herein, we report an adaptive supramolecular assembly via a multivalent co-assembly strategy prepared in two stages by using an adamantane-connected pyrenyl pyridinium derivative (APA2), sulfonated aluminum phthalocyanine (PcS), and folic acid-modified β-cyclodextrin (FA-CD) for efficient dual-organelle targeted photodynamic cancer cell ablation. Benefiting from π-π and electrostatic interactions, APA2 and PcS could first assemble into non-fluorescent irregular nanoaggregates because of the heterodimer aggregation-induced quenching and then secondarily assemble with FA-CD to afford targeted spherical nanoparticles (NPs) with an average diameter of around 50 nm, which could be specifically taken up by HeLa cancer cells through endocytosis in comparison with 293T normal cells. Intriguingly, such multivalent NPs could adaptively disaggregate in an intracellular physiological environment of cancer cells and further respectively and selectively accumulate in mitochondria and lysosomes, which not only displayed near-infrared two-organelle localization in situ but also aroused efficient singlet oxygen generation under light irradiation to effectively eliminate cancer cells up to 99%. This supramolecular multivalent assembly with an adaptive feature in a specific cancer cell environment provides a feasible strategy for precise organelle-targeted imaging and an efficiently synergetic photodynamic effect in situ for cancer cell ablation.

Targeted Multifunctional Nanoplatform for Imaging-Guided Precision Diagnosis and Photothermal/Photodynamic Therapy of Orthotopic Hepatocellular Carcinoma.

BackgroundEffective theranostic of hepatocellular carcinoma (HCC) in an early-stage is imminently demanded to improve its poor prognosis. Combination of the near-infrared (NIR) photoacoustic imaging (PAI) and fluorescence imaging (FLI) can provide high temporospatial resolution, outstanding optical contrast, and deep penetration and thus is promising for accurate and sensitive HCC diagnosis.MethodsA versatile CXCR4-targeted Indocyanine green (ICG)/Platinum (Pt)-doped polydopamine melanin-mimic nanoparticle (designated ICG/Pt@PDA-CXCR4, referred to as IPP-c) is synthesized as an HCC-specific contrast agent for high-resolution precise diagnostic PAI/FLI and optical imaging-guided targeted photothermal therapy (PTT)/photodynamic therapy (PDT) of orthotopic small hepatocellular carcinoma (SHCC).ResultsThe multifunctional targeted nanoparticle yields superior HCC specificity, high imaging contrast in both PAI and FLI, good stability, reliable biocompatibility, effective singlet oxygen generation and superior photothermal conversion efficiency (PCE, 58.7%) upon 808-nm laser irradiation. The targeting ability of IPP-c was validated in in vitro experiments on selectively killing the CXCR4-overexpressing HCC cells. Moreover, we test the efficient dual-modal optical precision diagnosis properties of IPP-c via in vivo experiments on targeted particle accumulation in an early-stage SHCC mouse model (tumor diameter about 1.2 mm). Then, under the guidance of real-time optical imaging, effective and mini-invasive PTT/PDT of orthotopic SHCCs were demonstrated without damaging adjacent liver tissues or other major organs.ConclusionThis study presented a multifunctional CXCR4-targeted nanoparticle to conduct effective and mini-invasive phototherapeutics of orthotopic SHCCs via the real-time quantitative guidance by optical imaging, which provided a new perception for building a versatile targeted nanoplatform for phototheranostics of early-stage HCC.

Highly efficient singlet oxygen generation of AIE luminogens enable mitochondria-targeted photodynamic therapy

The development of aggregation-induced emission luminogens (AIEgens) with high brightness and efficient photodynamic therapy (PDT) is of great value for the precise diagnosis and treatment of cancers. In this contribution, two novel AIEgens, TBBCyP and TBTCyP with D-A-π-A structure, were designed and prepared based on molecular rational design of electron-donating receptors. Experimental and theoretical results indicated that both TBBCyP and TBTCyP own bright AIE feature, satisfy photos ability, and generate efficient singlet oxygen (1O2). Notably, TBBCyP exhibited brighter emission and higher 1O2 yield in compared with TBTCyP, which could be ascribed to its weaker twisted intramolecular charge transfer (TICT) effect and narrower singlet-triplet energy gap (ΔEST). Moreover, it was proved that TBBCyP and TBTCyP showed a great mitochondrial specificity and desired intracellular ROS productivity for realizing the effective mitochondria-targeted PDT of cancer cells.

Asymmetric Phenyl Substitution: An Effective Strategy to Enhance the Photosensitizing Potential of Curcuminoids.

Curcumin has been demonstrated to exhibit photosensitized bactericidal activity. However, the full exploitation of curcumin as a photo-pharmaceutical active principle is hindered by fast deactivation of the excited state through the transfer of the enol proton to the keto oxygen. Introducing an asymmetry in the molecular structure through acting on the phenyl substituents is expected to be a valuable strategy to impair this undesired de-excitation mechanism competing with the therapeutically relevant ones. In this study, two asymmetric curcumin analogs were synthesized and characterized as to their electronic-state transition spectroscopic properties. Fluorescence decay distributions were also reconstructed. Their analysis confirmed the substantial stabilization of the fluorescent state with respect to the parent compound. Nuclear magnetic resonance experiments were performed with the aim of determining the structural features of the keto–enol ring and the strength of the keto–enol hydrogen bond. Electronic structure calculations were also undertaken to elucidate the effects of substitution on the features of the keto–enol semi-aromatic system and the proneness to proton transfer. Finally, their singlet oxygen-generation efficiency was compared to that of curcumin through the 9,10-dimethylanthracene fluorescent assay.

Multivalent Phthalocyanine-Based Cationic Polymers with Enhanced Photodynamic Activity for the Bacterial Capture and Bacteria-Infected Wound Healing.

The solubility and photosensitive activity of phthalocyanine are crucial to photodynamic antibacterial performance. However, highly conjugated phthalocyanine with high singlet oxygen generation efficiency tends to aggregate in aqueous environments, leading to poor solubility and photodynamic antibacterial activity. Herein, we propose a novel photodynamic antibacterial therapeutic platform by a phthalocyanine-based polymeric photosensitizer for the efficient healing of a bacteria-infected wound. A prepared phthalocyanine-based chain-transfer agent and a tertiary amino group-containing monomer are applied in the reversible addition-fragmentation chain-transfer polymerization for the preparation of the polymeric photosensitizer, which is subsequently quaternized to obtain a positively charged surface. This water-soluble phthalocyanine-based polymer can strongly concentrate on bacterial membranes via electrostatic interaction. The formed singlet oxygen by the phthalocyanine-based polymer after 680 nm light irradiation plays an essential role in killing the Gram-positive and Gram-negative bacteria. The study of antibacterial action indicates that this nanocomposite can cause irreversible damage to the bacterial membranes, which can cause cytoplasm leakage and bacterial death. Moreover, this therapeutic platform has excellent biocompatibility and the capacity to heal the wounds of bacterial infections. Experimental results indicate that the design strategy of this phthalocyanine-based polymer can extend the application of the hydrophobic photosensitizer in the biomedical field.

Enhancing the Theranostic Performance of Organic Photosensitizers with Aggregation-Induced Emission

ConspectusPhotodynamic therapy has been actively explored recently to combat various physiological disorders and diseases, including bacterial infections, inflammation, and cancer. As a noninvasive modality with high spatiotemporal selectivity, photodynamic therapy leverages photosensitizers, light, and reactive oxygen species to induce cytotoxicity and cell death. Specifically, upon light irradiation, photosensitizers harvest the incident light energy to generate highly reactive singlet oxygen species through photochemical reactions to disrupt the integrity of certain cellular components of the target cells. The extent to which the target cells can be damaged depends largely on the characteristics of photosensitizers. As such, the selection and design of photosensitizers are essential to ensuring effective and safe photodynamic therapy. Unfortunately, organic photosensitizers typically used in photodynamic therapy tend to suffer from a considerable reduction in singlet oxygen production when these molecules aggregate, significantly limiting the efficacy of photodynamic therapy. To address this issue, a different class of organic photosensitizers with aggregation-induced emission (AIE) characteristics, which exhibit bright fluorescence and enhanced photosensitizing activity only when they exist in an aggregated state, has been increasingly formulated for disease theranostic applications.In general, AIE photosensitizers can be designed on the basis of several major strategies. For example, AIE photosensitizers with efficient singlet oxygen generation can be formulated by minimizing their singlet–triplet energy gap via tuning the distribution of the highest occupied molecular orbital and the lowest unoccupied molecular orbital of the molecules. Simultaneously, through donor–acceptor engineering, AIE photosensitizers can be designed to have increased molar absorptivity, red-shifted absorption and emission wavelengths, and improved body clearance. In situ click synthesis can also be adopted to formulate AIE photosensitizers with suppressed dark toxicity. These design approaches can be optimized using artificial intelligence or machine learning, leading to higher throughput discovery of AIE photosensitizers with exceptional performance. Intriguingly, the therapeutic impact of AIE photosensitizers can be further strengthened by modulating their performance-related features, notably targeting specificity, target accumulation and retention, tissue penetration depth, stimulus responsivity, and theranostic modality. By precisely controlling these elements, multifunctional and biocompatible AIE photosensitizers with superior performance can be realized.Herein, we describe our recent efforts in designing and formulating organic AIE photosensitizers with improved theranostic efficacy and safety to treat bacterial infections and cancer. We first introduce different principles that can be adopted to guide the design of AIE photosensitizers. We then present various ways to strengthen the different performance-associated features of AIE photosensitizers. These include enhancement of the targeting specificity, target accumulation, and retention of AIE photosensitizers through metabolic engineering, enhancement of the tissue penetration depth of AIE photosensitizers through chemiexcitation and ionizing irradiation, enhancement of AIE photosensitization by suppressing intrinsic oxidative resistance, enhancement of the responsivity of AIE photosensitizers through stimulus-responsive building blocks, and enhancement of the overall theranostic performance of AIE photosensitizers through combinatorial therapy. Finally, we identify current challenges, potential opportunities, and future research directions for this emerging field. Through this Account, we seek to stimulate further interest and active collaborations in the development, theranostic applications, and clinical translation of organic AIE photosensitizers to treat different diseases.

Correlation between the Efficiency of Singlet Oxygen Generation and the Luminescence Parameters of Photosensitizers

Correlation between the Efficiency of Singlet Oxygen Generation and the Luminescence Parameters of Photosensitizers

Selective oxidation of ethyl lactate to ethyl pyruvate by a photocatalytic strategy under room temperature

Selective oxidation of ethyl lactate (EL) with molecular oxygen as oxidant is an alternative route to produce ethyl pyruvate (EP). However, to obtain pyruvate with high yield under mild conditions remains challenging due to the troublesome over oxidation issue. Here, a highly efficient photocatalytic strategy was firstly developed to obtain EP at room temperature. ZnIn sulfides (ZIS) with different Zn/In ratios were synthesized as the catalysts. Under the irradiation of visible light, 100% EL conversion with 88.4% EP yield could be obtained. The optimized ZIS catalyst shows the highest surface area (215.7 m2 g−1) as well as much higher separation and transport efficiency of the electron-hole pairs. Combining radical trapping experiments with characterization results, a reaction mechanism was proposed. The mild reaction conditions with efficient generation of singlet oxygen contribute the high yield of EP. Kinetic isotope experiments indicate that the cleavage of C(OH)−H bond probably was involved in the rate determining step.

Anionic Cyanine J-Type Aggregate Nanoparticles with Enhanced Photosensitization for Mitochondria-Targeting Tumor Phototherapy.

Cyanines have been widely used as the photosensitizers (PSs) in the biomedical field, but controlling their molecular aggregates in nanoparticles (NPs) remains a major challenge. Moreover, the impact of aggregate behaviors of cyanines on the photosensitization is still unclear. Herein, the first anionic cyanine PSs based on a tricyanofuran end group have been designed by achieving supramolecular J-type aggregates in NPs via counterion engineering. Our results indicate that J-type aggregates in NPs can not only bring significantly red-shifted emission, negatively charged surface, and high photostability, but also enable a significant 5-fold increase in singlet oxygen generation efficiency compared to that in the nonaggregate state, providing strong experimental evidence for the superiority of J-aggregates in enhancing photosensitization. Thus, combined with the mitochondria-targeting ability, the J-type aggregate NPs show remarkable in vivo antitumor phototheranostic efficacy, making them have a potential for clinical use.

Anionic Cyanine J‐Type Aggregate Nanoparticles with Enhanced Photosensitization for Mitochondria‐Targeting Tumor Phototherapy

AbstractCyanines have been widely used as the photosensitizers (PSs) in the biomedical field, but controlling their molecular aggregates in nanoparticles (NPs) remains a major challenge. Moreover, the impact of aggregate behaviors of cyanines on the photosensitization is still unclear. Herein, the first anionic cyanine PSs based on a tricyanofuran end group have been designed by achieving supramolecular J‐type aggregates in NPs via counterion engineering. Our results indicate that J‐type aggregates in NPs can not only bring significantly red‐shifted emission, negatively charged surface, and high photostability, but also enable a significant 5‐fold increase in singlet oxygen generation efficiency compared to that in the nonaggregate state, providing strong experimental evidence for the superiority of J‐aggregates in enhancing photosensitization. Thus, combined with the mitochondria‐targeting ability, the J‐type aggregate NPs show remarkable in vivo antitumor phototheranostic efficacy, making them have a potential for clinical use.

Effective Therapy of Drug-Resistant Bacterial Infection by Killing Planktonic Bacteria and Destructing Biofilms with Cationic Photosensitizer Based on Phosphindole Oxide.

Developing effective therapies to fight against biofilm-associated infection is extremely urgent. The complex environment of biofilm forces the bacteria to evade the elimination of antibiotics, resulting in recalcitrant chronic infections. To address this issue, a cationic antibacterial agent based on phosphindole oxide (β-PM-PIO) is designed and prepared. The unique molecular structure endows β-PM-PIO with aggregation-induced emission feature and efficient singlet oxygen generation ability. β-PM-PIO shows excellent visual diagnostic function to planktonic bacteria and biofilm. In addition, owing to the synergistic effect of phototoxicity and dark toxicity, β-PM-PIO can achieve superb antibacterial and antibiofilm performance against Gram-positive bacteria with less potential of developing drug resistance. Notably, β-PM-PIO also holds excellent anti-infection capacity against drug-resistant bacteria in vivo with negligible side effects. This work offers a promising platform to develop advanced antibacterial agents against multidrug-resistant bacterial infection.

Photovoltaic polymer Photosensitizer-Doped Nano-Therapeutic reagent for in vivo enhanced bioimaging guided photodynamic therapy

For tumor imaging guided photodynamic therapy process, the conundrum of achieving high fluorescence efficiency and singlet oxygen generation efficiency concurrently under the excitation condition of visible light has become a major obstacle to the integration of diagnosis and treatment. For lack of effective methods to resolve this issue, constructing a single photosensitizer with high quantum yield, efficient singlet oxygen generation, stable red emission, excellent photo-stability and low dark toxicity is challenging. In this research, the performance bottleneck is broken by designing an effective donor–acceptor system with excellent imaging and great photodynamic therapy capability through judiciously incorporating a novel polymer (J71) into a hydrophobic conjugated polymer, which is the first time of utilizing this celebrity photovoltaic material as a photosensitizer in photodynamic therapy process. Through fluorescence resonance energy transfer from conjugated polymer to J71, the singlet oxygen production rate of nanoparticles can be enhanced to 0.704. The nanoparticle also exhibits relatively high quantum yield of 0.255. The relatively strong singlet oxygen yield and relatively high fluorescence efficiency of nanoparticle was competitive with other inorganic and organic photosensitizers. Moreover, the J71 as a novel photosensitizer is a kind of 2D-conjugated polymer, which displayed promising photo-stability than traditional porphyrin photosensitizer. The prepared nanoparticles present all desired properties. A series of in vivo and in vitro results revealed the excellent fluorescence imaging capability and noteworthy anti-tumor ability, indicative of this system has great potential application in tumor imaging guided photodynamic therapy.

Click Synthesis Enabled Sulfur Atom Strategy for Polymerization‐Enhanced and Two‐Photon Photosensitization

AbstractFacile tailoring of photosensitizers (PSs) with advanced and synergetic properties is highly expected to broaden and deepen photodynamic therapy (PDT) applications. Herein, a catalyst‐free thiol–yne click reaction was employed to develop the sulfur atom‐based PSs by using the in situ formed sulfur “heavy atom effect” to enhance the intersystem crossing (ISC), while such an effect can be remarkably magnified by the polymerization. The introduction of a tetraphenylpyrazine‐based aggregation‐induced emission (AIE) unit was also advantageous in PS design by suppressing their non‐radiative decay to facilitate the ISC in the aggregated state. Besides, the resulting sulfur atom electron donor, together with a double‐bond π bridge and AIE electron acceptor, created a donor‐π‐acceptor (D‐π‐A) molecular system with good two‐photon excitation properties. Combined with the high singlet oxygen generation efficiency, the fabricated polymer nanoparticles exhibited an excellent in vitro two‐photon‐excited PDT towards cancer cells, therefore possessing a huge potential for the deep‐tissue disease therapy.