Bithiophene-Functionalized Infrared Two-Photon Absorption Metal Complexes as Single-Molecule Platforms for Synergistic Photodynamic, Photothermal, and Chemotherapy.

A planar conjugated ligand functionalized with bithiophene and its Ru(II), Os(II), and Ir(III) complexes have been constructed as single-molecule platform for synergistic photodynamic, photothermal, and chemotherapy. The complexes have significant two-photon absorption at 808 nm and remarkable singlet oxygen and superoxide anion production in aqueous solution and cells when exposed to 808 nm infrared irradiation. The most potent Ru(II) complex Ru7 enters tumor cells via the rare macropinocytosis, locates in both nuclei and mitochondria, and regulates DNA-related chemotherapeutic mechanisms intranuclearly including DNA topoisomerase and RNA polymerase inhibition and their synergistic effects with photoactivated apoptosis, ferroptosis and DNA cleavage. Ru7 exhibits high efficacy in vivo for malignant melanoma and cisplatin-resistant non-small cell lung cancer tumors, with a 100% survival rate of mice, low toxicity to normal cells and low residual rate. Such an infrared two-photon activatable metal complex may contribute to a new generation of single-molecule-based integrated diagnosis and treatment platform to address drug resistance in clinical practice and phototherapy for large, deeply located solid tumors.

[Rapamycin and HPPH Co-Loaded Nanodrug Delivered via Dissolvable Microneedles to Treat Port-Wine Stains]. / å ±è½½é›·å¸•éœ‰ç´ å’Œå ‰å ‹æ´›çš„çº³ç±³è¯ç‰©å¤åˆå¯æº¶è§£å¾®é’ˆæ²»ç–—é²œçº¢æ–‘ç—£çš„å®žéªŒç ”ç©¶.

Objective: Port-wine stains are a kind of dermatological disease of congenital capillary malformation. Based on the biological characteristics of port-wine stains and the advantages of microneedle transdermal administration, we intend to construct a nanodrug co-loaded with rapamycin (RPM), an anti-angiogenesis drug, and photochlor (HPPH), a photosensitizer, and integrate the nanodrug with dissolvable microneedles (MN) to achieve anti-angiogenesis and photodynamic combination therapy for port-wine stains. Methods: First, RPM and HPPH co-loaded nanoparticles (RPM-HPPH NP) were prepared by the emulsification solvent-volatilization method, and its ability to generate reactive oxygen species (ROS) was investigated under 660 nm laser irradiation. Mouse hemangioendothelioma endothelial cells (EOMA) were used as the subjects of the study. The cellular uptake behaviors were examined by fluorescence microscopy and flow cytometry. The cytotoxicity effects of RPM-HPPH NP with or without 660 nm laser irradiation on EOMA cells were examined by MTT assays (with free RPM serving as the control). Then, hyaluronic acid (HA) dissolvable microneedles loaded with RPM-HPPH NP (RPM-HPPH NP@HA MN) were obtained by compounding the nanodrug with HA dissolvable microneedle system through the molding method. The morphological characteristics and mechanical properties of RPM-HPPH NP@HA MN were investigated by scanning electron microscope and electronic universal testing machine. The penetration ability of RPM-HPPH NP@HA MN on the skin of nude mice was evaluated by trypan blue staining and H&E staining experiment. Results: The RPM-HPPH NP prepared in the study had a particle size of 150 nm and generated large amounts of ROS under laser irradiation. At the cellular level, RPM-HPPH NP was taken up by EOMA cells in a time-dependent manner. The cytotoxicity of RPM-HPPH NP was higher than that of free RPM with or without laser irradiation. Under laser irradiation, RPM-HPPH NP exhibited stronger cytotoxic effects and the difference was statistically significant (P<0.05). The height of the needle tip of RPM-HPPH NP@HA MN was 600 µm and the mechanical property of a single needle was 0.75048 N. Trypan blue staining and HE staining showed that pressing on the microneedles could produce pores on the skin surface and penetration of the stratum corneum. Conclusion: RPM-HPPH NP@HA MN can deliver RPM-HPPH NP percutaneously to the lesion tissue and realize the synergistic treatment of port-wine stains with anti-angiogenic therapy and photodynamic therapy, providing a new strategy for the construction of nanodrug-loaded microneedle delivery system and the clinical treatment of port-wine stains.

Donor-Acceptor Modulating of Ionic AIE Photosensitizers for Enhanced ROS Generation and NIR-II Emission.

Photosensitizers (PSs) with aggregation-induced emission (AIE) characteristics are competitive candidates for bioimaging and therapeutic applications. However, their short emission wavelength and non-specific organelle targeting hinder their therapeutic effectiveness. Herein, we report a donor-acceptor modulation approach to construct a series of ionic AIE photosensitizers with enhanced photodynamic therapy (PDT) outcomes and fluorescent emission in the second near-infrared (NIR-II) window. By employing dithieno[3,2-b:2',3'-d]pyrrole (DTP) and indolium (In) as the strong donor and acceptor, respectively, the compound DTP-In exhibits a substantial redshift in absorption and fluorescent emission reach to NIR-II region. The reduced energy gap between singlet and triplet states in DTP-In also increases the reactive oxygen species (ROS) generation rate. Further, DTP-In can self-assemble in aqueous solutions, forming positively charged nanoaggregates, which are superior to conventional encapsulated nanoparticles in cellular uptake and mitochondrial targeting. Consequently, DTP-In aggregates show efficient photodynamic ablation of 4T1 cancer cells and outstanding tumor theranostic in vivo under 660 nm laser irradiation. This work highlights the potential of molecular engineering of donor-acceptor AIE PSs with multiple functionalities, thereby facilitating the development of more effective strategies for cancer therapy. This article is protected by copyright. All rights reserved.

Quasi-intrinsic thiobase derivatives as potential targeted photosensitizers in two-photon photodynamic therapy.

In this study, a set of potential quasi-intrinsic photosensitizers for two-photon photodynamic therapy (PDT) are proposed based on the unnatural 2-amino-8-(1'-ß-ᴅ-2'-deoxyribofuranosyl)-imidazo[1,2-ɑ]-1,3,5-triazin-4(8H)-one (P), which is paired with the 6-amino-5-nitro-3-(1'-ß-ᴅ-2'-deoxyribofuranosyl)-2(1H)-pyridone (Z) and can specifically recognize breast and liver cancer cells. Herein, the effects of sulfur substitution and electron-donating/electron-withdrawing groups on the photophysical properties in aqueous solution are systematically investigated. The one- and two-photon absorption spectra evidence that the modifications could result in red-shifted absorption wavelength and large two-photon absorption cross-section, which contributes to selective excitation and provides effective PDT for deep-seated tissues. To ensure the efficient triplet state population, the singlet-triplet energy gaps and spin-orbit coupling constants were examined, which is responsible for a rapid intersystem crossing rate. Furthermore, these thiobase derivatives are characterized by the long-lived T1 state and the large energy gap for radiationless transition to ensure the generation of cytotoxic singlet oxygen.

Therapeutic and fluorescence evaluation of 20% 5-aminolevulinic acid-mediated photodynamic therapy in actinic keratosis.

BACKGROUND: Actinic keratosis (AK) is a precancerous lesion that occurs in areas that are chronically exposed to sunlight and has the potential to develop into invasive cutaneous squamous cell carcinoma (cSCC). We investigated the efficacy of 20% 5-aminolevulinic acid-photodynamic therapy (ALA-PDT) with LED red light for the treatment of AK in Chinese patients by examining changes in dermoscopic features, histopathology and fluorescence after treatment. METHODS: Twenty-eight patients with fourty-six AK lesions from March 2022 to September 2023 were treated with 20% ALA, and 3 hours later, they were irradiated with LED red light (80-100 mW/cm2) for 20 minutes. A session of 20% ALA-PDT was performed once a week for three consecutive weeks, and the dermoscopic, histopathological, fluorescent and photoaging outcomes were measured one week after the treatment. RESULTS: One week after ALA-PDT, complete remission (CR) was reached in 53.6% of patients. The CR of Grade I AK lesions was 100%, that of Grade II lesions was 71.4%, and that of Grade III lesions was 38.1%. There was a significant improvement in the dermoscopic features, epidermal thickness and fluorescence of the AK lesions. The presence of red fluorescence decreased, and there was an association between CR and post-PDT fluorescence intensity. ALA-PDT also exhibited efficacy in treating photoaging, including fine lines, sallowness, mottled pigmentation, erythema, and telangiectasias, and improved the global score for photoaging. There were no serious adverse effects during or after ALA-PDT, and 82.1% of the patients were satisfied with the treatment. CONCLUSION: AK lesions can be safely and effectively treated with 20% ALA-PDT with LED red light, which also alleviates photoaging in Chinese patients, including those with multiple AKs. This study highlights the possibility that fluorescence could be used to diagnose AK with peripheral field cancerization and evaluate the efficacy of ALA-PDT.

Site-selective antibody-lipid conjugates for surface functionalization of red blood cells and targeted drug delivery.

Displaying antibodies on carrier surfaces facilitates precise targeting and delivery of drugs to diseased cells. Here, we report the synthesis of antibody-lipid conjugates (ALCs) through site-selective acetylation of Lys 248 in human Immunoglobulin G (IgG) and the development of antibody-functionalized red blood cells (immunoRBC) for targeted drug delivery. ImmunoRBC with the HER2-selective antibody trastuzumab displayed on the surface (called Tras-RBC) was constructed following a three-step procedure. First, a peptide-guided, proximity-induced reaction transferred an azidoacetyl group to the ε-amino group of Lys 248 in the Fc domain. Second, the azide-modified IgG was subsequently conjugated with dibenzocyclooctyne (DBCO)-functionalized lipids via strain-promoted azide-alkyne cycloaddition (SPAAC) to result in ALCs. Third, the lipid portion of ALCs was then inserted into the cell membranes, and IgGs were displayed on red blood cells (RBCs) to construct immunoRBCs. We then loaded Tras-RBC with a photosensitizer (PS), Zinc phthalocyanine (ZnPc), to selectively target HER2-overexpressing cells, release ZnPc into cancer cells following photolysis, and induce photodynamic cytotoxicity in the cancer cells. This work showcases assembling immunoRBCs following site-selective lipid conjugation on therapeutic antibodies and the targeted introduction of PS into cancer cells. This method could apply to the surface functionalization of other membrane-bound vesicles or lipid nanoparticles for antibody-directed drug delivery.

Photoinactivation Effects of Curcumin, Nano-curcumin, and Erythrosine on Planktonic and Biofilm Cultures of Streptococcus mutans.

Introduction: This in vitro study was conducted to assess the phototoxic effects of curcumin, nano-curcumin, and erythrosine on the viability of Streptococcus mutans (S. mutans) in suspension and biofilm forms. Methods: Various concentrations of curcumin (1.5 g/L, 3 g/L), nano-curcumin (3 g/L), and erythrosine (100 µM/L, 250 µM/L) were examined for their impact on planktonic and biofilm cultures of S. mutans, either individually or in conjunction with light irradiation (photodynamic therapy or PDT). A blue light-emitting diode (LED) with a central wavelength of 450 nm served as the light source. The results were compared to 0.12% chlorhexidine digluconate (CHX) as the positive control, and a solution containing neither a photosensitizer (PS) nor a light source as the negative control group. The dependent variable was the number of viable microorganisms per experiment (CFU/mL). Results: Antimicrobial PDT caused a significant reduction in the viability of S. mutans in both planktonic and biofilm forms, compared to the negative control group (P<0.05). The highest cell killing was observed in PDT groups with curcumin 3 g/L or erythrosine 250 µmol/L, although the difference with PDT groups using curcumin 1.5 g/L or erythrosine 100 µmol/L was not significant (P>0.05). Antimicrobial treatments were more effective against planktonic S. mutans than the biofilm form. Conclusion: PDT with either curcumin 1.5 g/L or erythrosine 100 µmol/L may be suggested as an alternative to CHX to inactivate the bacteria in dental plaque or deep cavities. Nano-curcumin, at the selected concentration, exhibited lower efficacy in killing S. mutans compared to Curcumin or erythrosine.

Hybrid adipocyte-derived exosome nano platform for potent chemo-phototherapy in targeted hepatocellular carcinoma.

The high prevalence and severity of hepatocellular carcinoma (HCC) present a significant menace to human health. Despite the significant advancements in nanotechnology-driven antineoplastic agents, there remains a conspicuous gap in the development of targeted chemotherapeutic agents specifically designed for HCC. Consequently, there is an urgent need to explore potent drug delivery systems for effective HCC treatment. Here we have exploited the interplay between HCC and adipocyte to engineer a hybrid adipocyte-derived exosome platform, serving as a versatile vehicle to specifically target HCC and exsert potent antitumor effect. A lipid-like prodrug of docetaxel (DSTG) with a reactive oxygen species (ROS)-cleavable linker, and a lipid-conjugated photosensitizer (PPLA), spontaneously co-assemble into nanoparticles, functioning as the lipid cores of the hybrid exosomes (HEMPs and NEMPs). These nanoparticles are further encapsuled within adipocyte-derived exosome membranes, enhancing their affinity towards HCC cancer cells. As such, cancer cell uptakes of hybrid exosomes are increased up to 5.73-fold compared to lipid core nanoparticles. Our in vitro and in vivo experiments have demonstrated that HEMPs not only enhance the bioactivity of the prodrug and extend its circulation in the bloodstream but also effectively inhibit tumor growth by selectively targeting hepatocellular carcinoma tumor cells. Self-facilitated synergistic drug release subsequently promoting antitumor efficacy, inducing significant inhibition of tumor growth with minimal side effects. Our findings herald a promising direction for the development of targeted HCC therapeutics.

Efficacy of interstitial photodynamic therapy using talaporfin sodium and a semiconductor laser for a mouse allograft glioma model.

To investigate the therapeutic potential of photodynamic therapy (PDT) for malignant gliomas arising in unresectable sites, we investigated the effect of tumor tissue damage by interstitial PDT (i-PDT) using talaporfin sodium (TPS) in a mouse glioma model in which C6 glioma cells were implanted subcutaneously. A kinetic study of TPS demonstrated that a dose of 10 mg/kg and 90 min after administration was appropriate dose and timing for i-PDT. Performing i-PDT using a small-diameter plastic optical fiber demonstrated that an irradiation energy density of 100 J/cm2 or higher was required to achieve therapeutic effects over the entire tumor tissue. The tissue damage induced apoptosis in the area close to the light source, whereas vascular effects, such as fibrin thrombus formation occurred in the area slightly distant from the light source. Furthermore, when irradiating at the same energy density, irradiation at a lower power density for a longer period of time was more effective than irradiation at a higher power density for a shorter time. When performing i-PDT, it is important to consider the rate of delivery of the irradiation light into the tumor tissue and to set irradiation conditions that achieve an optimal balance between cytotoxic and vascular effects.

In Vitro Exploration of Dark Cytotoxicity of Anthocyanin-Curcumin Combination, A Herbal Photosensitizer.

BACKGROUND: Photodynamic therapy can be used to treat a variety of lesions noninvasively, including oral cancer. High-power laser therapy has also been used to treat oral squamous cell carcinomas. The two main components of photodynamic treatment are the photosensitizer and the light source. Herbal formulations of photosensitizers are used to mask the disadvantages of other photosensitizers. METHODOLOGY: A methanol-diluted 25 grams of Punica granatum was used to create an anthocyanin extract using the flash evaporation method. Dimethyl sulfoxide (DMSO) was used as the first dilution agent for curcumin; later further dilution was done with distilled water. Following that, MCF-7 cells (a cancer cell line) were cultured with the produced samples, and the mono-tetrazolium salt (MTT) assay was used to determine the vitality of the cells. RESULTS: Cell reduction was significantly evident in all three groups, but the most significant cell death was found in the anthocyanin-curcumin group, at 29%. CONCLUSION: The combination of anthocyanin-curcumin has one of the photophysical properties (dark cytotoxicity) and hence can aid as a photosensitizer.

Enhancing cancer immunotherapy with photodynamic therapy and nanoparticle: making tumor microenvironment hotter to make immunotherapeutic work better.

Cancer immunotherapy has made tremendous advancements in treating various malignancies. The biggest hurdle to successful immunotherapy would be the immunosuppressive tumor microenvironment (TME) and low immunogenicity of cancer cells. To make immunotherapy successful, the 'cold' TME must be converted to 'hot' immunostimulatory status to activate residual host immune responses. To this end, the immunosuppressive equilibrium in TME should be broken, and immunogenic cancer cell death ought to be induced to stimulate tumor-killing immune cells appropriately. Photodynamic therapy (PDT) is an efficient way of inducing immunogenic cell death (ICD) of cancer cells and disrupting immune-restrictive tumor tissues. PDT would trigger a chain reaction that would make the TME 'hot' and have ICD-induced tumor antigens presented to immune cells. In principle, the strategic combination of PDT and immunotherapy would synergize to enhance therapeutic outcomes in many intractable tumors. Novel technologies employing nanocarriers were developed to deliver photosensitizers and immunotherapeutic to TME efficiently. New-generation nanomedicines have been developed for PDT immunotherapy in recent years, which will accelerate clinical applications.

Antimicrobial Activity of Methylene Blue Associated with Photodynamic Therapy: In Vitro Study in Multi-Species Oral Biofilm.

The control of infectious diseases caused by biofilms is a continuing challenge for researchers due to the complexity of their microbial structures and therapeutic implications. Photodynamic therapy as an adjunctive anti-infective treatment has been described as a possible valid approach but has not been tested in polymicrobial biofilm models. This study evaluated the effect of photodynamic therapy in vitro with methylene blue (MB) 0.01% and red LEDs (λ = 660 nm, power density ≈ 330 mW/cm2, 2 mm distance from culture) on the metabolic activity and composition of a multispecies subgingival biofilm. Test Groups LED and MB + LED showed a more significant reduction in metabolic activity than the non-LED application group (~50 and 55%, respectively). Groups LED and MB equally affected (more than 80%) the total bacterial count in biofilms. No differences were noted in the bacterial biofilm composition between the groups. In vitro LED alone or the MB + LED combination reduced the metabolic activity of bacteria in polymicrobial biofilms and the total subgingival biofilm count.

Multimodal phototherapy agents target lipid droplets for near-infrared imaging-guided type I photodynamic/photothermal therapy.

The construction and optimization of a single phototherapeutic agent with photoluminescence, type I photodynamic therapy (PDT), and photothermal therapy (PTT) functions remain challenging. In this study, we aimed to design and synthesize four donor-acceptor (D-A) type aggregation-induced emission molecules: PSI, TPSI, PSSI, and TPSSI. We employed phenothiazine as an electron donor and 1,3-bis(dicyanomethylidene)indan as a strong electron acceptor in the synthesis process. Among them, TPSSI exhibited efficient type I reactive oxygen species generation, high photothermal conversion efficiency (45.44 %), and near-infrared emission. These observations can be attributed to the introduction of a triphenylamine electron donor group and a thiophene unit, which resulted in increased D-A strengths, a reduced singlet-triplet energy gap, and increased free intramolecular motion. TPSSI was loaded into bovine serum albumin to prepare biocompatible TPSSI nanoparticles (NPs). Our results have indicated that TPSSI NPs can target lipid droplets with negligible dark toxicity and can efficiently generate O2•- in hypoxic tumor environments. Moreover, TPSSI NPs selectively targeted 4T1 tumor tissues and exhibited a good PDT-PTT synergistic effect in vitro and in vivo. We believe that the successful preparation of multifunctional phototherapeutic agents will promote the development of efficient tumor diagnosis and treatment technologies. STATEMENT OF SIGNIFICANCE: The construction of a single phototherapeutic agent with photoluminescence, type I photodynamic therapy, and photothermal therapy functions, and its optimization remain challenging. In this study, we construct four donor-acceptor aggregation-induced emission molecules using phenothiazine as an electron donor and 1,3-Bis(dicyanomethylidene)indan as a strong electron acceptor. By optimizing the molecular structure, an integrated phototherapy agent with fluorescence imaging ability and high photodynamic / photothermal therapy performance was prepared. We believe that the successful preparation of multifunctional phototherapeutic agents will promote the development of efficient tumor diagnosis and treatment technology.

In Vitro Modeling of Recurrent Dermatofibrosarcoma Protuberans: Assessment of 5-Aminolevulinic Acid Photodynamic Therapy Efficacy.

BACKGROUND: Dermatofibrosarcoma Protuberans (DFSP) is a rare, low-grade malignant tumor of the dermis with a high recurrence rate post-surgery. Current treatments, including surgery, radiotherapy, and targeted therapy, have limitations. Photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA) is a promising non-invasive approach, but its efficacy in DFSP treatment remains underexplored. METHODS: This study aimed to evaluate the anti-tumor efficacy of 5-ALA PDT using an in vitro model derived from a recurrent DFSP patient. The cells were treated with varying concentrations of 5-ALA and exposed to red light, followed by assessments of cell viability, proliferation, apoptosis, migration, invasion, angiogenesis, and expression of DFSP-related genes and proteins. RESULTS: 5-ALA PDT significantly reduced DFSP cell viability in a dose-dependent manner and induced apoptosis. It also effectively inhibited cell proliferation, migration, and invasion, as well as suppressed angiogenic activity in conditioned media. Furthermore, 5-ALA PDT downregulated the expression of COL1A1 and PDGFRB, key genes in DFSP pathogenesis. CONCLUSIONS: The findings provide the first evidence of 5-ALA PDT's in vitro anti-tumor efficacy against DFSP, suggesting its potential as a novel therapeutic approach for DFSP. Further studies are warranted to explore the clinical utility of 5-ALA PDT in preventing DFSP recurrence.

Photodynamic Effect of Vascular-targeted Polyphenol Nanoparticles on Endothelial Cells.

BACKGROUND: Port wine stains (PWS) are vascular malformations, and photodynamic therapy (PDT) is a promising treatment. Emerging drug delivery method employs nanoparticles (NPs) to enhance drug permeability and retention in diseased blood vessels and improving drug bioavailability. (-) -epigallocatechin-3-gallate glycine (EGCG) has anti-angiogenetic effects and boosts photodynamic therapy. Chlorin e6 (Ce6) is capable of efficiently producing singlet oxygen, rendering it a very promising photosensitizer for utilization in nanomedicine. MATERIAL AND METHODS: EGCG-Ce6-NPs were synthesized and characterized using various techniques. The photodynamic effects of EGCG-Ce6-NPs on endothelial cells were evaluated. The compatibility and toxicity of the nanoparticle was tested using the CCK-8 assay. The intracellular uptake of the nanoparticle was observed using an inverted fluorescence microscope, and the intracellular fluorescence intensity was detected using flow cytometry. The ROS generation and apoptosis induced by EGCG-Ce6-NPs was observed using confocal laser scanning microscope and flow cytometry respectively. RESULTS: EGCG-Ce6-NPs exhibited stability, spherical shape of uniform size while reducing the particle diameter, low polydisperse profile and retaining the ability to effectively generate singlet oxygen. These characteristics suggest promising potential for enhancing drug permeability and retention. Additionally, EGCG-Ce6-NPs demonstrated good compatibility with endothelial cells and enhanced intracellular uptake of Chlorin e6. Furthermore, EGCG-Ce6-NPs increased activation efficiency, induced significant toxicity, more reactive oxygen species, and higher rate of late apoptosis after laser irradiation. CONCLUSION: This in vitro study showed the potentials EGCG-Ce6-NPs for the destruction of endothelial cells in vasculature.

An update on alternative therapy for Escherichia coli causing urinary tract infections; a narrative review.

BACKGROUND: Urinary tract infections (UTIs) are the most common type of nosocomial infection and severe health issues because of the difficulties and frequent recurrence. Today, alternative methods such as sonodynamic therapy (SDT), photodynamic therapy (PDT) and herbal materials use for treating infections like UTI in many countries. METHOD: We conducted searches of the biomedical databases (Google Scholar, Scopus, PubMed, and Web of sciences) to identify related studies from 2008 to 2023. RESULT: SDT aims to use ultrasound to activate a sonosensitizer, which causes a biological effect by raising reactive oxygen species (ROS). When bacteria are exposed to ROS, several important effects occur: oxidative damage, DNA damage, protein dysfunction etc. SDT with herbal medicine significantly reduced the number of colony-forming units and bactericidal activity for Klebsiella pneumonia and E. coli. PDT is a promising treatment for cancer and microbial infections, combining a photosensitiser, light and tissue molecular oxygen. It involves a photosensitizer, light source, and oxygen, with variations affecting microbial binding and bactericidal activity. Factors affecting antibacterial properties include plant type, growing conditions, harvesting, and processing. This review highlights the recent advancements in sonodynamic, photodynamic, herbal, and bio-material-based approaches in the treatment of E. coli infections. CONCLUSIONS: These alternative therapies offer exciting prospects for addressing UTIs, especially in cases where traditional antibiotic treatments may be less effective. Further research and clinical studies are warranted to fully explore the potential of these innovative treatment modalities in combating UTIs and improving patient outcomes.

Correlation of in vitro cell viability and cumulative singlet oxygen luminescence from protoporphyrin IX in mitochondria and plasma membrane.

SIGNIFICANCE: Photodynamic therapy (PDT) can be targeted toward different subcellular localizations, and it is proposed that different subcellular targets vary in their sensitivity to photobiological damage. Since singlet oxygen (1O2) has a very short lifetime with a limited diffusion length in cellular environments, measurement of cumulative 1O2 luminescence is the most direct approach to compare the PDT sensitivity of mitochondria and plasma membrane. APPROACH: PDT-generated near-infrared 1O2 luminescence at 1270 nm was measured together with cell viability for 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) and exogenous PpIX, at different incubation times. Confocal fluorescence microscopy indicated that ALA-induced PpIX (2 h) localized in the mitochondria, whereas exogenous PpIX (1 h) mainly localized to the plasma membrane. Cell viability was determined at several time points during PDT treatments using colony-forming assays, and the surviving fraction correlated well with cumulative 1O2 luminescence counts from PpIX in mitochondria and plasmas membrane, respectively. RESULTS: The mitochondria are more sensitive than the plasma membrane by a factor of 1.7. CONCLUSIONS: Direct 1O2 luminescence dosimetry's potential value for comparing the PDT sensitivity of different subcellular organelles was demonstrated. This could be useful for developing subcellular targeted novel photosensitizers to enhance PDT efficiency.

Low-level photodynamic therapy in chronic wounds.

BACKGROUND: Chronic wounds refer to those that can't reconstruct anatomical and physical functional integrity, and are usually associated with signs of microbial infection. Current therapies include debridement and dressing change, local or systemic application of antibiotics, and medical dressing care, which are not ideal for the healing of chronic wounds. OBJECTIVE: To explore the efficacy and safety of photodynamic therapy (ALA-PDT) for the treatment of chronic infectious wounds. MATERIALS AND METHODS: ALA-PDT was used in ten patients with persistent wound infections and systemic complications who did not respond to conventional treatment. 5 % ALA solution was applied to the wound surface after debridement, incubated for 3 h with light protection, and then irradiated with red light for 20 min. This procedure was repeated every two weeks, and any adverse reactions were recorded. After the end of three treatments, the patients were followed up for 3 months. RESULTS: Patients who exhibit resistance to traditional therapies demonstrate a favorable therapeutic outcome with ALA-PDT, although complications may impede wound healing. All participants successfully underwent ALA-PDT treatment and subsequent monitoring, with 90 % achieving complete healing. Common adverse reactions to ALA-PDT encompass treatment-related pain, temporary erythema, and swelling, all of which are well-tolerated by patients without enduring severe consequences. CONCLUSIONS: ALA-PDT proves to be an efficacious intervention for managing chronic wounds, irrespective of the presence of localized infections or systemic complications.

Photodynamic therapy for recalcitrant plantar warts: Case reports and a literature review.

Plantar wart is one of the most recalcitrant types of cutaneous warts with a high recurrence rate. Recalcitrant plantar warts are resistant to traditional treatments such as cryotherapy. Photodynamic therapy (PDT) is a modern, non-invasive method utilized to treat benign and malignant skin disorders. Several previous studies have reported the effective application of PDT treatment for plantar warts. We reported three cases of recalcitrant plantar warts successfully treated with PDT.

Photodynamic anticancer activity evaluation of novel 5-aminolevulinic acid and 3-hydroxypyridinone conjugates.

5-Aminolevulinic acid (ALA) and its derivatives, serving as the endogenous precursor of the photosensitizer (PS) protoporphyrin IX (PpIX), successfully applied in tumor imaging and photodynamic therapy (PDT). ALA and its derivatives have been used to treat actinic keratosis (AK), basal cell carcinoma (BCC), and improve the detection of superficial bladder cancer. However, the high hydrophilicity of ALA and the conversion of PpIX to heme have limited the accumulation of PpIX, hindering the efficiency and potential application of ALA-PDT. This study aims to evaluate the PDT activity of three rationally designed series of ALA-HPO prodrugs, which were based on enhancing the lipophilicity of the prodrugs and reducing the labile iron pool (LIP) through HPO iron chelators to promote PpIX accumulation. Twenty-four ALA-HPO conjugates, incorporating amide, amino acid, and ester linkages, were synthesized. Most of the conjugates, exhibited no dark-toxicity to cells, according to bioactivity evaluation. Ester conjugates 19a-g showed promoted phototoxicity when tested on tumor cell lines, and this increased phototoxicity was strongly correlated with elevated PpIX levels. Among them, conjugate 19c emerged as the most promising (HeLa, IC50 = 24.25 ± 1.43 µM; MCF-7, IC50 = 43.30 ± 1.76 µM; A375, IC50 = 28.03 ± 1.00 µM), displaying superior photodynamic anticancer activity to ALA (IC50 > 100 µM). At a concentration of 80 µM, the fluorescence intensity of PpIX induced by compound 19c in HeLa, MCF-7, and A375 cells was 18.9, 5.3, and 2.8 times higher, respectively, than that induced by ALA. In conclusion, cellular phototoxicity showed a strong correlation with intracellular PpIX fluorescence levels, indicating the potential application of ALA-HPO conjugates in ALA-PDT.