Photosensitizer Research Articles

A pH stable fluoran-triphenylamine photosensitizer with efficient type I and type II ROS generation.

Photosensitizers (PSs) with robust pH stability and the ability to generate both type I and type II reactive oxygen species (ROS) have gained significant attention due to their versatility in various applications. In this study, we employed an electron donor-acceptor engineering strategy to design and synthesize a fluoran-triphenylamine photosensitizer (Fl-TPA), using an ester-protected ring-opened fluoran cation as the electron acceptor and triphenylamine (TPA) as the electron donor. Compared to fluoran with a spirolactone structure, Fl-TPA exhibits a significant redshift in absorption, with good light capture capabilities in the 300-600 nm range. In comparison with the reference compound Fl-H, which lacks the TPA group, Fl-TPA shows a substantial decrease in fluorescence intensity. Transient fluorescence measurements reveal biexponential decay characteristics for both compounds. Specifically, Fl-TPA shows τ1 = 0.21 ns (41%) and τ2 = 2.92 ns (59%), while Fl-H shows τ1 = 0.14 ns (93%) and τ2 = 2.23 ns (7%). The longer-lived component in Fl-TPA is more pronounced, suggesting the presence of additional non-radiative decay pathways, as further supported by the steady-state fluorescence analysis. Additionally, Fl-TPA exhibits a significant Stokes shift in solvents of varying polarity. Time-dependent density functional theory (TD-DFT) calculations reveal that the introduction of the strong electron-donating TPA group reduces the ΔES-T of Fl-TPA to 1.25 eV, which is significantly lower than that of Fl-H (1.46 eV), facilitating intersystem crossing (ISC). Thus, in the ROS generation experiment, it can be observed that Fl-H produces almost no ROS. In contrast, Fl-TPA not only exhibits high type I ROS generation capability, but also demonstrates excellent type II and total ROS generation capabilities, with performance far superior to the clinically approved near-infrared PS, indocyanine green (ICG). Moreover, Fl-TPA exhibits excellent pH stability compared to the non-esterified fluoran. The results of this study present a new photosensitizer with strong ROS generation capability and good stability across a wide pH range, providing a theoretical foundation for the design of PSs.

Cancer stem cell populations are resistant to 5-aminolevulinic acid-photodynamic therapy (5-ALA-PDT)

Photodynamic therapy (PDT) is a minimally invasive treatment approved for many types of cancers. PDT involves the administration of photoactive substances called photosensitizers (PS) that selectively accumulate in cancer cells and are subsequently excited/activated by irradiation with light at wavelengths of optimal absorbance. Activated PS leads to the generation of singlet oxygen and other reactive oxygen species (ROS), promoting cancer cell death. 5-aminolevulinic acid (5-ALA) is a naturally occurring PS precursor, which is metabolically converted to the PS, protoporphyrin IX (PPIX). Although 5-ALA-PDT is effective at killing cancer cells, in prior studies conducted by our group we normally observed in in vitro experiments that approximately 5–10% of cells survive 5-ALA-PDT, which served as an impetus for further investigation. Identifying the mechanisms of resistance to 5-ALA-PDT-mediated cell death is important to prevent tumor recurrence following 5-ALA-PDT. Previously, we reported that oncogenic activation of Ras/MEK promotes PPIX efflux and reduces cellular sensitivity to 5-ALA-PDT through increased expression of ABCB1 transporter. As cancer stem cells (CSCs) are known to drive resistance to other cancer treatments and have high efflux of chemotherapeutic agents via ABC-family transporters, we hypothesize that CSCs underlie 5-ALA-PDT resistance. In this study, we determined (1) if CSCs are resistant to 5-ALA-PDT and (2) if CSCs play roles in establishing resistant populations of 5-ALA-PDT. When we compared CSC populations before and after 5-ALA-PDT, we found that CSCs were less susceptible to 5-ALA-PDT. Moreover, we found that the CSC population was enriched in 5-ALA-PDT-resistant cell lines compared to the parental cell line. Our results indicate that CSCs are not sensitive to 5-ALA-PDT, which may contribute to establishment of 5-ALA-PDT resistance.

Diplatinum Single-Molecular Photocatalyst Capable of Driving Hydrogen Production from Water via Singlet-to-Triplet Transitions.

Solar-driven hydrogen production is regarded as one of the most ideal methods to achieve a sustainable society. In order to artificially establish efficient photosynthetic systems, efforts have been made to develop single-molecular photocatalysts capable of serving both as a photosensitizer (PS) and a catalyst (Cat) in hydrogen evolution reaction (HER). Although examples of such hybrid molecular photocatalysts have been demonstrated in the literature, their solar energy conversion efficiencies still remain quite limited. Here we demonstrate that a new dinuclear platinum(II) complex Pt2(bpia)Cl3(bpia = bis(2-pyridylimidoyl)amido) serves as a single-molecular photocatalyst for HER with its performance significantly higher than that of the PtCl(tpy)- and PtCl2(bpy)-type photocatalysts developed in our group (tpy = 2,2': 6',2''-terpyridine, bpy = 2,2'-bipyridine). The outstanding feature is that Pt2(bpia)Cl3 can produce H2 even by irradiating the lower-energy light above 500 nm, which is rationalized due to the direct population of triplet states via singlet-to-triplet transitions (i.e., S-T transitions) accelerated by the diplatinum core.To the best of our knowledge, Pt2(bpia)Cl3 is the first example of a single-molecular photocatalyst enabling hydrogen production from water via the S-T transitions using lower-energy light (> 580 nm).

Diplatinum Single‐Molecular Photocatalyst Capable of Driving Hydrogen Production from Water via Singlet‐to‐Triplet Transitions

Solar‐driven hydrogen production is regarded as one of the most ideal methods to achieve a sustainable society. In order to artificially establish efficient photosynthetic systems, efforts have been made to develop single‐molecular photocatalysts capable of serving both as a photosensitizer (PS) and a catalyst (Cat) in hydrogen evolution reaction (HER). Although examples of such hybrid molecular photocatalysts have been demonstrated in the literature, their solar energy conversion efficiencies still remain quite limited. Here we demonstrate that a new dinuclear platinum(II) complex Pt2(bpia)Cl3 (bpia = bis(2‐pyridylimidoyl)amido) serves as a single‐molecular photocatalyst for HER with its performance significantly higher than that of the PtCl(tpy)‐ and PtCl2(bpy)‐type photocatalysts developed in our group (tpy = 2,2′: 6′,2′′‐terpyridine, bpy = 2,2′‐bipyridine). The outstanding feature is that Pt2(bpia)Cl3 can produce H2 even by irradiating the lower‐energy light above 500 nm, which is rationalized due to the direct population of triplet states via singlet‐to‐triplet transitions (i.e., S‐T transitions) accelerated by the diplatinum core. To the best of our knowledge, Pt2(bpia)Cl3 is the first example of a single‐molecular photocatalyst enabling hydrogen production from water via the S‐T transitions using lower‐energy light (> 580 nm).

Advancements in photodynamic inactivation: A comprehensive review of photosensitizers, mechanisms, and applications in food area.

Food microbial contamination results in serious food safety issues and numerous food loss and waste, presenting one of the most significant challenges facing the global food system. Photodynamic inactivation (PDI) technology, which combines light and photosensitizers (PS) to provide antimicrobial effects, is an ideal nonthermal antimicrobial technique for the food industry. This review provides a comprehensive overview of PDI technology, beginning with the fundamental photoactivation principles of PS and the pathways of photoinduced reactive oxygen species (ROS) generation. PS is the most critical factor affecting PDI efficiency, which is categorized into three types: organic, metal oxide-, and carbon-based. This review systemically summarizes the photophysical properties, in vitro PDI performances, potential enhancement strategies, and the advantages and limitations of each type of PS. Furthermore, the antimicrobial mechanisms of the PDI technologies are analyzed at both microscopic and molecular levels. Finally, the current applications of PDI in various food systems are discussed, along with the associated challenges and opportunities. Overall, this review offers crucial insights into optimizing and advancing PDI technology, highlighting key challenges and suggesting future research directions to enhance the effectiveness and scalability of PDI for diverse food applications.

Micro‐Engraving UV‐Sensitive Thin‐Film Transistor from Metal–Metal Oxide Nanoparticles with Band‐Gap Engineering

AbstractAs known, n‐type inorganic semiconductor nanoparticles such as zinc oxide nanoparticles have been explored in various sensing applications, which demand high‐density electronic elements placement for rapid operation. Herein, high‐resolution designs of conductive channels of noble metal‐doped zinc oxide nanoparticles is demonstrated using an engraving transfer printing process and silver metal doping approach. Such thin‐film transistors with reduced feature size to 2 µm fabricated exhibited significantly enhanced electron mobility up 3.46 × 10−2 cm2 V−1 s−1 and light sensitivity. Furthermore, the integration of this micropatterning technology and metal doping in thin‐film transistors is utilized for control of current–voltage characteristics under the ultraviolet radiation with high sensitivity. It is suggested that this approach to design of doped inorganic nanoparticle channels paves the way for high‐density thin‐film transistors suitable for optoelectronic circuit, UV photodetectors and neuromorphic computing systems.

Topographic correlation of microperimetry with foveal microstructure characteristics in idiopathic epiretinal membrane patients with an ectopic inner foveal layer

PurposeTo identify foveal structure-function topographic association and relationship in patients with idiopathic epiretinal membrane (ERM) related to ectopic inner foveal layer (EIFL).MethodsThis was a cross-sectional, observational study that involved 40 individuals with idiopathic ERM: 22 without EIFL (Group 1) and 18 with EIFL (Group 2). Quantitative foveal light sensitivity was measured using microperimetry, and foveal microstructure was assessed using spectral-domain optical coherence tomography (SD-OCT) and optical coherence tomography angiography (OCTA). Multiple indices of microvascular parameters of OCTA images were further processed using the AngioTool software. LASSO regression and quantile regression analyses were performed to identify the spatial distribution correlation between foveal light sensitivity and foveal microstructure parameters.ResultsGroup 2 exhibited reduced light sensitivity across all parameters of microperimetry compared to Group 1 (P < 0.001). Additionally, the central foveal thickness, the percentage of ellipsoid zone disruption, and the foveal avascular zone area were significantly lower in Group 1 than in Group 2 (all P < 0.005). Compared to Group 1, the vessel density (VD) and perfusion density of the foveal region was significantly increased in Group 2 (P < 0.001). In contrast, Group 2 showed significantly decreased VD in the parafoveal region compared with Group 1 (P < 0.05). Significant differences in OCTA parameters including ‘total number of junctions’, ‘junction density’, ‘total vessel length’, ‘average vessel length’, ‘total number of end points’ were observed between Group 1 and Group 2 (all P < 0.01). The foveal light sensitivity was significantly positively correlated with VD in the parafoveal region and negatively correlated with EIFL alteration, best-corrected visual acuity and ellipsoid zone disruption [Log(λ) = − 0.18303, λ = 0.6561].ConclusionsThe presence of EIFL and decreased VD in the parafoveal region, factors that collectively elevate the risk of disease progression, are significantly and independently correlated with reduced microperimetric retinal sensitivity in patients with idiopathic ERM.

Dyad System of BOAHY-BODIPY Conjugates as Novel Photoswitchable Photosensitizers for Photodynamic Therapy.

Photodynamic therapy (PDT) offers minimally invasive and repeatable cancer treatment options. Despite advancements in photosensitizer (PS) design, the optical control of PS activation remains unexplored. Here, we present the first photoswitchable PS based on a BOAHY-BODIPY dyad system. Inspired by BODIPY multimer structures and BOAHY's photoisomerization properties, we designed mono-(4 series) and bis-BOAHY-BODIPY (5 series) conjugates. These dyads primarily generate reactive oxygen species via a type-I process under white light. Notably, the 4 series compounds demonstrated effective photocytotoxicity and photoswitching properties in vitro. Building on these, we iodinated the monoconjugates to develop the highly efficient photoswitching PS, 6b, which exhibited enhanced intersystem crossing and type-II reactive oxygen species generation due to a reduced singlet-triplet energy gap. As the first demonstration of photoswitchable PDT agents, this strategy introduces a new approach with significant potential for selective cancer treatment and clinical applications.

Transition metal complexes: next-generation photosensitizers for combating Gram-positive bacteria.

The rise of antibiotic-resistant Gram-positive bacterial infections poses a significant threat to public health, necessitating the exploration of alternative therapeutic strategies. A photosensitizer (PS) can convert energy from absorbed photon into reactive oxygen species (ROS) for damaging bacteria. This photoinactivation action bypassing conventional antibiotic mechanism is less prone to resistance development, making antibacterial photodynamic therapy (aPDT) highly efficient in combating Gram-positive bacteria. Photodynamic transition metal complexes leveraging the unique properties of metals to enhance the aPDT activity are the next-generation PS. This review provides an overview of metal-based PS for combating Gram-positive bacteria. Based on the structures, these metal-PS could be mainly classified as metal-tetrapyrrole derivatives, ruthenium complexes, iridium complexes, and zinc complexes. PS based on complexes of other transition metals such as silver, cobalt, and rhenium are also presented. Finally, we summarize the advantages and shortcomings of these metal- PS, conclude some critical aspects impacting their aPDT performances and give a perspective on their future development.

Chlorin e6: a promising photosensitizer of anti-tumor and anti-inflammatory effects in PDT.

Photodynamic therapy (PDT) involves the activation of photosensitizers (PSs) by visible laser light at the target site to catalyze the production of reactive oxygen species, resulting in tumor cell death and blood vessel closure. The efficacy of PDT depends on the PSs, the amount of oxygen, and the intensity of the excitation laser. PSs have been extensively researched, and great efforts have been made to develop an ideal photosensitizer. Chlorin-e6 is an FDA-approved second-generation PSs that has attracted widespread research interest in the medical field, especially with respect to antitumor and anti-inflammatory activity. Chlorin-e6 possesses the advantages of a large absorption coefficient, high strength, low residue in the body, and relatively high safety and thus has promising application prospects. Here we review the use of chlorin-e6 in PDT and discuss the prospects of further development of this technology.

Construction of Photosensitizer Candidates in Photodynamic Therapy: Computer Aided Design, Calculation, and Screening.

Thiophene and pyrrole units are extensively utilized in light-responsive materials and have significantly advanced the field of organic photovoltaics (OPV). This progress has inspired our exploration of photosensitizers (PS) for photodynamic therapy (PDT). Currently, traditional PS face limitations in clinical application, including a restricted variety and narrow applicability. Drawing upon molecular design concepts from OPV, we aim to transcend these limitations in PDT. Given the abundance of candidate molecules, effective screening is crucial. Theoretical calculations and electronic structure analyses serve as precise and practical screening methods. In this study, we adopted strategies successfully employed in OPV molecular design, focusing on donor-acceptor (D-A) and acceptor-donor-acceptor (A-D-A) structures. Using density functional theory (DFT) and time-dependent density functional theory (TDDFT), we systematically designed combinations of promising organic fragments. These fragments include polythiophene and polypyrrole-dominated donor structures, paired with five electron acceptors: indene (Ind), diketopyrrole (DPP), naphthalimide (Ni), benzothiazole (Btd), and dithiazolyl diketopyrrole (Tbo). Through meticulous calculations, we obtained electronic structures and spectral properties for all candidate molecules, facilitating an efficient screening process. Our findings highlight that those combinations of polypyrrole-based frameworks with DPP, Ni, and Btd show significant promise for PS applications. Approximately 13% of candidates were selected through comprehensive comparison, markedly reducing molecular design time and experimental costs. This interdisciplinary approach holds potential to pave the way for more targeted and successful PS designs.

Impact of repeated low-level red-light therapy on axial length, refraction, and macular retinal blood flow density in adolescents with mild to moderate myopia.

In order to evaluate the effectiveness of repeated low-level red-light (RLRL) therapy on stabilizing axial elongation and refractive changes in adolescents with mild to moderate myopia. In addition, we also examined whether RLRL therapy affects retinal blood flow density in the macular region, a factor previously unstudied in this context. Conducted at a single clinical site, this retrospective, single-arm study followed participants over six months, with assessments at baseline, 1 month, 3 months, and 6 months. The primary outcomes included axial length and spherical equivalent refraction (SER) changes. Secondary assessments included retinal blood flow density (superficial and deep macular layers), white-to-white corneal diameter, central corneal thickness, intraocular pressure (IOP), corneal curvature, light sensitivity, and peripheral retinal thickness. There were 32 enrolled participants (mean age = 11.5 ± 1.72) in the current study. The spherical equivalent (SER) remained relatively stable over the first three months, but it significantly improved at six months, changing from -2.39 ± 2.21 D at baseline to -2.01 ± 2.12 D (P < 0.05). However, the axial length also showed minimal variation across follow-up visits, indicating stable eye growth with no substantial elongation throughout the study period. Furthermore, RLRL therapy resulted in stable measurements across primary and secondary outcomes (all P > 0.05), with no significant changes over the six months. There were no obvious side effects following the treatment. Low-energy red light therapy shows promise as a non-invasive approach for stabilizing myopia in adolescents, with no observed compromise to retinal blood flow density. Further longitudinal research is needed to validate these findings and support clinical recommendations for myopia management.

Development of optical microneedle–lens array for photodynamic therapy

Recently, photodynamic therapy (PDT) which involves a photosensitizer (PS), a special drug activated by light, and light irradiation has been widely used in treating various skin diseases such as port-wine stain as well as cancers such as melanoma and non-melanoma skin cancers. PDT comprises two general steps: the introduction of PS into the body or a specific spot to be treated, and the irradiation process using a light source with a specific wavelength to excite the PS. Although PDT is gaining great attention owing to its potential as a targeted approach in the treatment of skin cancers, several limitations still exist for practical use. One of the biggest challenges is the limited penetration of light owing to scattering, reflection, and absorption of light inside the skin layers. In addition, accidental light exposure of the target area causes additional cellular damage, which causes unexpected complications. To solve these issues, we introduced an optical microneedle–lens array (OMLA) to improve the efficiency and safety of PDT treatment. We designed and fabricated a novel optical microneedle–lens array with controlled dimensions to optimize light transmission. In addition, PS was coated uniformly over the tips of the OMLA using the dip coating method. Finally, we confirmed that the PS coated on the OMLA was released into the target area and subsequently generated radical oxygen by light irradiation. We expect that our proposed OMLA for PDT treatment can realize a new light-transmission platform optimized for PDT with targeting various types of skin cancers.Graphical abstract

In vitro evaluation of antimicrobial photodynamic therapy with photosensitizers and calcium hydroxide on bond strength, chemical composition, and sealing of glass-fiber posts to root dentin

Investigate the impact of antimicrobial photodynamic therapy (aPDT) using different photosensitizers (PSs) such as indocyanine green (IG), curcumin (CC), and methylene blue (MB), with or without intracanal application of calcium hydroxide (CH), on the push-out bond strength of glass-fiber posts (GFPs) to intraradicular dentin, the chemical composition of the root substrate, and the sealing of the adhesive interface across different thirds of intraradicular dentin. A total of 112 bovine teeth underwent biomechanical preparation and were divided into eight experimental groups (n = 14 each): Negative control with deionized water; positive control with deionized water + CH; IG group with indocyanine green and infrared laser; IG + CH group; CC group with curcumin and blue LED; CC + CH group; MB group with methylene blue and red laser; and MB + CH group. The push-out bond strength was measured using a universal testing machine (n = 8), and scanning electron microscopy characterized the fracture patterns. Energy dispersive spectroscopy (n = 3) analyzed the chemical composition of the dentin substrate, while fluorescence confocal microscopy (n = 3) assessed the adhesive interface sealing between the resin cement and root dentin. Data were analyzed using two-way repeated measures ANOVA and the Tukey test for push-out bond strength and chemical composition comparison, with the Kruskal-Wallis and Dunn’s tests (α = 0.05) for adhesive interface sealing. Significant bond strength differences were noted across root thirds and experimental groups (P < .05), with the IG + CH group showing the highest cervical bond strength and the IG group the lowest. Apical bond strength was highest in the CC group but lower in the NC and PC groups. Mixed failures predominated, except in the MB + CH group, where adhesive failures prevailed. Elemental composition varied among groups treated with different PSs and CH (P < .05), but interface quality, tag formation, and penetration depth showed no significant differences (P > .05). Laser-activated 500 mg/L CC combined with CH emerged as a clinically relevant option for root canal decontamination before GFPs luting. aPDT with different PSs and root canal depth influenced the push-out bond strength of GFPs and the chemical composition of root dentin. Curcumin-mediated aPDT at 500 mg/L proved effective, enhancing bond strength and sealing while maintaining consistent dentin composition across depths.

Spontaneously Photocatalytic Nanoplatform for Sensitive Diagnosis and Penetrated Therapy of Cancer.

In this study, a sensitive diagnosis and spontaneously photocatalytic therapy of cancer based on chemiluminescence (CL) and nanozyme was studied. Briefly, carbon nitride-supported copper nanoparticles (CuCNs) loaded with luminol (CuCN-L) were utilized to develop a microneedle patch (CuCN-L/MN). The CuCN-L probe could target overexpressed H2O2 in the TME and actively emit CL to achieve cancer cell imaging for diagnosis. In addition, 425 nm blue-violet CL could photocatalyze CuCN to reduce carbon dioxide (CO2) to carbon monoxide (CO) for gas therapy (GT). Meanwhile, CuCN, acting as a photosensitizer (PS), could be activated by CL to produce reactive oxygen species (ROS), which realized photodynamic therapy (PDT). Furthermore, the use of a degradable MN based on hyaluronic acid (HA) promotes painless local administration as well as deep administration of GT and PDT. This technology of optical sensor-mediated anticancer treatment will have great potential to provide new inspirations for cancer diagnosis and therapy based on a self-excited nanoplatform.

Cataract Eye Disease Diagnosis Using the Random Forest Method

This study developed a machine learning-based classification model using the Random Forest algorithm to detect cataract risk based on 11 variables: age, gender, family history, lens opacity, visual acuity reduction, light sensitivity, color changes, double vision, intraocular pressure, slit-lamp results, and visual acuity. Feature importance analysis revealed that lens opacity and visual acuity variables contributed most significantly to cataract risk prediction, followed by intraocular pressure and visual acuity reduction. The system was designed using Google Colab for model training and Streamlit as an interactive interface, enabling real-time predictions with intuitive result visualization. After optimization using Grid Search, the model achieved an accuracy of 92.0%, precision of 95.0%, sensitivity of 90.0%, F1 Score of 92.4%, and specificity of 98.0%. This system is expected to serve as an effective supporting tool for medical professionals in the early diagnosis of cataracts.

Heterodimeric Photosensitizer as Radical Generators to Promoting Type I Photodynamic Conversion for Hypoxic Tumor Therapy.

Photodynamic therapy (PDT) using traditional type II photosensitizers (PSs) has been limited in hypoxic tumors due to excessive oxygen consumption. The conversion from type II into a less oxygen-dependent type I PDT pathway has shown the potential to combat hypoxic tumors. Herein, the design of a heterodimeric PS, NBSSe, by conjugating a widely used type I PS NBS and a type II PS NBSe via molecular dimerization, achieving the aggregation-regulated efficient type I photodynamic conversion for the first time is reported. Electrochemistry characterizations and theoretical calculations elucidate that NBSSe tends to form a S+·/Se-· radical pair via intramolecular electron transfer in the co-excited NBSSe* aggregate, realizing 7.25-fold O2 -· generation compared to NBS and 80% suppression of 1O2 generation compared to NBSe. The enhanced O2 -· generation of NBSSe enables excellent anti-hypoxia PDT efficiency and inhibition of pulmonary metastasis. Additionally, the incorporation of electron-rich bovine serum albumin accelerates the recycling of cationic PS radical NBSSe+·, further boosting photostability and O2 -· generation. The resultant BSA@NBSSe nanoparticles demonstrate successful tumor-targeting PDT capability. This work provides an appealing avenue to convert ROS generation from the type II pathway to the type I pathway for efficient cancer phototherapy in hypoxia.

Ex Vivo Biosafety and Efficacy Assessment of Advanced Chlorin e6 Nanoemulsions as a Drug Delivery System for Photodynamic Antitumoral Application

The photosensitizer (PS) in the Photodynamic Therapy (PDT) field represents a key factor, being directly connected to the therapeutic efficacy of the process. Chlorin e6 is a second-generation photosensitizer, approved by the FDA with the most desired clinical properties for PDT applications, presenting high reactive oxygen species (ROS) generation and proven anticancer properties. However, hydrophobicity is a major limitation, leading to poor biodistribution. To overcome this condition, the present work developed an up-to-date nanoemulsion incorporating Ce6 in a new nanosystem (Ce6/NE). A comprehensive study of physicochemical properties, stability, fluorescence characteristics, the in vitro release profile, in vivo and ex vivo biocompatibility, and ex vivo efficacy was established. The nanoemulsions showed the desired particle size and stability over six months, with no spectroscopic or photophysical alterations. Uptake studies demonstrated the internalization of the Ce6/NE in monolayers, with biocompatibility at the lowest concentrations. The HET-CAM assay, however, revealed a higher biocompatibility range, also indicating Ce6/NE’s potential for cancer treatment through antiangiogenic studies. These findings highlight the use of a new promising photosensitizer for PDT modulated with nanotechnology that promotes low toxicity, higher bioavailability, and site-specific delivery.

Triphenylamine‐Substituted Nile Red Derivatives with Efficient Reactive Oxygen Species Generation for Robust and Broad‐Spectrum Antimicrobial Photodynamic Therapy and Abscess Wound Healing

AbstractInfections caused by drug‐resistant bacteria represent a major contributor to high mortality rates, underscoring the urgent need for effective non‐antibiotic drugs and alternative therapies. Antimicrobial photodynamic therapy (aPDT) emerges as an innovative treatment due to its minimal drug resistance. Herein, a series of Nile Red derivatives is synthesized by a donor engineering strategy. Notably, NTPA featuring triphenylamine (TPA) as the electron‐donating group, exhibited the highest production of reactive oxygen species (ROS). The enhanced electron donating‐accepting (D‐A) property effectively reduced the energy gap between S1 and T1 (ΔES‐T), facilitating intersystem crossing (ISC) with a larger spin‐orbit coupling (SOC) constant. Furthermore, the twisted conformation profoundly suppressed the quenching of ROS. As expected, an over 470‐fold increase in ROS production is observed, predominantly comprising type‐I ROS. NTPA nanoparticles (NPs) exhibited exceptional in vitro killing ability against various drug‐resistant bacteria, with inhibition efficiency even reaching 99.9%. In the methicillin‐resistant staphylococcus aureus (MRSA)‐induced abscess model, NTPA NPs facilitated complete wound healing within just 8 days following a single administration and irradiation, highlighting their exceptional bactericidal and wound‐healing promotion capabilities. Overall, this work inspired the construction of efficient Nile Red‐based type‐I photosensitizers (PSs) and the development of a new broad‐spectrum aPDT method for drug‐resistant bacteria treatment.

Bioorthogonal reaction-mediated photosensitizer-peptide conjugate anchoring on cell membranes for enhanced photodynamic therapy.

Photodynamic therapy (PDT), utilizing a photosensitizer (PS) to induce tumor cell death, is an effective modality for cancer treatment. PS-peptide conjugates have recently demonstrated remarkable antitumor potential in preclinical trials. However, the limited cell membrane binding affinity and rapid systemic clearance have hindered their transition to clinical applications. To address these challenges, we investigated whether in vivo covalent chemistry could enhance tumor accumulation and potentiate antitumor efficacy. Specifically, we synthesized a PS-peptide conjugate termed P-DBCO-Ce6, with chlorin e6 (Ce6) and dibenzocyclooctyne (DBCO) conjugated to a negatively charged short peptide. By employing metabolic glycoengineering and bioorthogonal reactions, P-DBCO-Ce6 achieves covalent bonding to the cell membrane, enabling prolonged retention of the PS on the cell surface and the in situ generation of reactive oxygen species (ROS) on cell membranes to kill tumor cells. In vivo studies demonstrated a 3.3-fold increase in tumor accumulation of the PS through bioorthogonal reactions compared to the control group, confirming that click chemistry can effectively enhance PS tumor accumulation. This approach allows for the effective elimination of tumors with a single treatment. The improved efficiency of this strategy provides new insights into the design of PDT systems for potential clinical applications.