Codelivery of anti-CD47 antibody and chlorin e6 using a dual pH-sensitive nanodrug for photodynamic immunotherapy of osteosarcoma.

Osteosarcoma is a malignant tumor originating from bone tissue that progresses rapidly and has a poor patient prognosis. Immunotherapy has shown great potential in the treatment of osteosarcoma. However, the immunosuppressive microenvironment severely limits the efficacy of osteosarcoma treatment. The dual pH-sensitive nanocarrier has emerged as an effective antitumor drug delivery system that can selectively release drugs into the acidic tumor microenvironment. Here, we prepared a dual pH-sensitive nanocarrier, loaded with the photosensitizer Chlorin e6 (Ce6) and CD47 monoclonal antibodies (aCD47), to deliver synergistic photodynamic and immunotherapy of osteosarcoma. On laser irradiation, Ce6 can generate reactive oxygen species (ROS) to kill cancer cells directly and induces immunogenic tumor cell death (ICD), which further facilitates the dendritic cell maturation induced by blockade of CD47 by aCD47. Moreover, both calreticulin released during ICD and CD47 blockade can accelerate phagocytosis of tumor cells by macrophages, promote antigen presentation, and eventually induce T lymphocyte-mediated antitumor immunity. Overall, the dual pH-sensitive nanodrug loaded with Ce6 and aCD47 showed excellent immune-activating and anti-tumor effects in osteosarcoma, which may lay the theoretical foundation for a novel combination model of osteosarcoma treatment.

Evaluation of antifungal activity of visible light-activated doped TiO2 nanoparticles.

Titanium dioxide (TiO2) is a well-known material for its biomedical applications, among which its implementation as a photosensitizer in photodynamic therapy has attracted considerable interest due to its photocatalytic properties, biocompatibility, high chemical stability, and low toxicity. However, the photoactivation of TiO2 requires ultraviolet light, which may lead to cell mutation and consequently cancer. To address these challenges, recent research has focused on the incorporation of metal dopants into the TiO2 lattice to shift the band gap to lower energies by introducing allowed energy states within the band gap, thus ensuring the harnessing of visible light. This study presents the synthesis, characterization, and application of TiO2 nanoparticles (NPs) in their undoped, doped, and co-doped forms for antimicrobial photodynamic therapy (APDT) against Candida albicans. Blue light with a wavelength of 450 nm was used, with doses ranging from 20 to 60 J/cm2 and an NP concentration of 500 µg/ml. It was observed that doping TiO2 with Cu, Fe, Ag ions, and co-doping Cu:Fe into the TiO2 nanostructure enhanced the visible light photoactivity of TiO2 NPs. Experimental studies were done to investigate the effects of different ions doped into the TiO2 crystal lattice on their structural, optical, morphological, and chemical composition for APDT applications. In particular, Ag-doped TiO2 emerged as the best candidate, achieving 90-100% eradication of C. albicans.

Photodynamic Therapy Combined with Liquid Nitrogen Cryotherapy and Curettage for the Treatment of Recalcitrant Periungual and Subungual Warts: Clinical Experience and Literature Review.

Warts are caused by human papillomavirus (HPV) infection and can involve multiple parts of skin and mucosa, of which periungual and subungual warts are the most difficult to treat. Periungual or subungual wart is verruca vulgaris growing around or under the fingernail, destroying and deforming the nail and nail bed. Currently, liquid nitrogen cryotherapy and CO2 laser are often used for the treatment. Clinically, few doctors routinely use photodynamic therapy (PDT) to treat viral warts. We used PDT combined with liquid nitrogen cryotherapy and curettage to successfully treat a case of intractable periungual and subungual warts.

Harnessing antimicrobial peptide-coupled photosensitizer to combat drug-resistant biofilm infections through enhanced photodynamic therapy.

Bacterial biofilm-associated infection was one of the most serious threats to human health. However, effective drugs for drug-resistance bacteria or biofilms remain rarely reported. Here, we propose an innovative strategy to develop a multifunctional antimicrobial agent with broad-spectrum antibacterial activity by coupling photosensitizers (PSs) with antimicrobial peptides (AMPs). This strategy capitalizes on the ability of PSs to generate reactive oxygen species (ROS) and the membrane-targeting property of AMPs (KRWWKWIRW, a peptide screened by an artificial neural network), synergistically enhancing the antimicrobial activity. In addition, unlike conventional aggregation-caused quenching (ACQ) photosensitizers, aggregation-induced emission (AIE) PSs show stronger fluorescence emission in the aggregated state to help visualize the antibacterial mechanism. In vitro antibacterial experiments demonstrated the excellent killing effects of the developed agent against both Gram-positive (G+) and Gram-negative (G-) bacteria. The bacterial-aggregations induced ability enhanced the photoactivatable antibacterial activity against G- bacteria. Notably, it exhibited a significant effect on destroying MRSA biofilms. Moreover, it also showed remarkable efficacy in treating wound infections in mice in vivo. This multifunctional antimicrobial agent holds significant potential in addressing the challenges posed by bacterial biofilm-associated infections and drug-resistant bacteria.

Recent Advances on Diarylethene-Based Photoswitching Materials: Applications in Bioimaging, Controlled Singlet Oxygen Generation for Photodynamic Therapy and Catalysis.

Diarylethenes (DAE), a class of best performing photoswitchable compounds, where the key features of stability, photoisomerization wavelengths, quantum yield and variability in the photoisomers significantly depend on their derivatization. The last decade has witnessed a surge in the engagement of DAEs to different areas of chemical and biological impacts like catalysis in synthetic organic chemistry, biological markers for in vivo imaging of live cells, chemosensing within cells to photo-dynamic therapy by controlled generation of singlet oxygen. Previous reviews on applications of DAE-based systems did not predominantly cover all the aspects of biological and industrial implementations. They have covered only one field of application either in the biological science or the synthetic aspect or photochromic aspects only. This review is a coalition of all those aspects in last six years. Here the variation of properties of the DAE systems with respect to structural diversifications have been discussed in detail along with their potential applications in catalysis, regulating singlet oxygen generation, photodynamic therapy, bioimaging and their future prospects. We hope that this review will certainly motivate researchers to generate new DAE architectures with superior bioimaging or catalyzing properties in future.

Recent advances in photosensitizer materials for light-mediated tumor therapy.

Photodynamic therapy (PDT) as an emerging therapeutic method has drawn many attentions in the treatment field for cancer. Photosensitizer, which can convert photon energy into cytotoxic species under light irradiation, is the core component in PDT. The design of photosensitizers still faces problems of light absorption, targeting, penetration and oxygen dependence. With the rapid progress of material science, various photosensitizers have been developed to produce cytotoxic species for treatment of tumor with high selectivity, safety, and noninvasiveness. Besides, the applications of photosensitizers have been expanded to diverse cancer treatments such as drug release, optogenetics and immune checkpoint blockade. In this review, we summarize the recent advances of photosensitizers in various therapeutic methods for cancer. Prevailing challenges and further prospects associated with photosensitizers are also discussed.

Simulating PDT of port-wine stains in the in vivo chicken wattle model using Hemoporfin and radiation at 532 nm: Comparison of a LED and a laser source.

Port-wine stain (PWS) birthmarks are congenital capillary malformations occurring in 0.3 %∼0.5 % of newborns. Hemoporfin-mediated vascular-acting photodynamic therapy (Hemoporfin PDT) is an emerging option for treating PWS. This in vivo study aimed to compare laser and light-emitting diodes (LED) as light source for Hemoporfin PDT. Chicken wattles were used as the animal model. Color and histopathological changes were evaluated after combining Hemoporfin with KTP laser or LED light source of 532 nm at the same doses. Both PDT approaches could induce significant vascular injury and color bleaching. Although the use of the laser resulted in a greater vascular clearance, the LED showed more uniform distribution both in the beam profiles and tissue reaction and exhibited better safety. This in vivo study suggests that the LED is a favorable choice for larger PWS lesion.

Melanin-Ce6-Loaded Polydopamine Nanoparticles-Based Enhanced Phototherapy for B16 Melanoma Cancer Cells.

Melanoma is one of the most aggressive and lethal types of cancer owing to its metastatic propensity and chemoresistance property. An alternative therapeutic option is Photodynamic and Photothermal Therapies (PDT/PTT), which employ near-infrared light to generate heat and Reactive Oxygen Species (ROS). As per previous reports, Melanin and its synthetic analogs (i.e., polydopamine nanoparticles) can induce near-infrared (NIR) light-mediated heat energy, thereby selectively targeting and ameliorating cancer cells. Similarly, Chlorin e6 (Ce6) also has high ROS generation ability and antitumor activity against various types of cancer. Based on this tenet, In the current study, we have encapsulated Mel-Ce6 in a Polydopamine (PDA) nanocarrier (MCP NPs) synthesized by the oxidation polymerization method. The hydrodynamic diameter of the synthesized spherical MCP NPs was 139 ± 10 nm. The MCP NPs, upon irradiation with NIR 690 nm laser for 6 minutes, showed photothermal efficacy of more than 50 °C. Moreover, the red fluorescence in the MCP NPs due to Ce6 can be leveraged for diagnostic purposes. Further, the MCP NPs exhibited considerable biocompatibility with the L929 cell line and nearly 70% ROS-mediated cytotoxicity on the B16 melanoma cell line after the laser exposure. Thus, the prepared MCP NPs could be a promising theragnostic agent for treating the B16 melanoma cancer. .

Multi-targets of antimicrobial photodynamic therapy mediated by erythrosine against Staphylococcus aureus identified by proteomic approach.

Staphylococcus aureus is a global challenge to the clinical field and food industry. Therefore, the development of antimicrobial photodynamic therapy (aPDT) has become one of the valuable methods to control this pathogen. The antibacterial activity of photoinactivation by erythrosine (Ery) against S. aureus has been reported, but its modes of action are unclear. This study aimed to employ a proteomic approach to analyze modes of action of Ery-aPDT against S. aureus. We determined the antibacterial effect by Ery-aPDT assays, quantified reactive oxygen species (ROS) and injury to the cell membrane, and determined protein expression using a proteomic approach combined with bioinformatic tools. Ery-aPDT was effective in reducing S. aureus to undetectable levels. In addition, the increment of ROS accompanied the increase in the reduction of cell viability, and damage to cellular membranes was shown by sublethal injury. In proteomic analysis, we found 17 differentially expressed proteins. These proteins revealed changes mainly associated with defense to oxidative stress, energy metabolism, translation, and protein biosynthesis. Thus, these results suggest that the effectiveness of Ery-aPDT is due to multi-targets in the bacterial cell that cause the death of S. aureus.

Extramammary Paget Disease. Part II. Evidence-based Approach to Management.

Extramammary Paget disease is a rare cutaneous malignancy that most commonly affects the genitals, perianal area, and axilla of elderly patients. Delays in care often lead to high levels of disease burden for patients. Thus, evidence-based recommendations are paramount in mitigating morbidity and mortality for this unique patient population. This 2-part continuing medical education series provides a complete picture of extramammary Paget disease. Part 2 of this continuing medical education series focuses on the complex management of extramammary Paget disease including surgical and non-invasive therapies, as well as novel approaches for advanced disease.

Neuroimmunomodulatory Effect of NO on Chronic Wound Healing After Photodynamic Therapy.

Neuroimmunomodulation is the capacity of the nervous system to regulate immune processes. The existence of neurotransmitter receptors in immune cells enables this phenomenon to take place. Neuronal mediators possess the capacity to direct and control several occurrences during the wound healing process. Nitric oxide (NO) functions as a neuromodulator, playing a crucial role in the regulation of vascular tone and blood pressure with antimicrobial properties. Photodynamic therapy has been shown to augment the function of immune cells involved in the healing process of venous leg ulcers. Nitric oxide can be secreted into the extracellular environment by these cells. In lesions treated with PDT, the synthesis of iNOs (the enzyme that releases NO) increased, as demonstrated by the experimental results. Therefore the significance of PDT in enhancing the clinical condition of the lesion is thus highlighted.

Hybrid Sono-Photodynamic Combination Therapy Mediated by Water-Soluble Gallium Phthalocyanine Enhances the Cytotoxic Effect against Breast Cancer Cell Lines.

Breast cancer is a life-threatening disease that is gaining increasing importance due to its rising incidence, highlighting the need for novel treatment methods with the least disadvantages. Recently, scientists have focused on developing therapeutic treatment modalities for effective cancer treatment. In contrast to conventional cancer treatment methods such as immunotherapy, surgery, chemotherapy, or radiotherapy, photodynamic therapy (PDT) is gaining prominence. Besides, sonodynamic treatment (SDT) is a noninvasive therapeutic approach that uses ultrasound to induce high tissue penetration. In both methods, sensitizers are activated to generate cytotoxic reactive oxygen species such as •OH and 1O2. In particular, the combined use of hybrid and complementary treatment methods has become an important modality in cancer treatment in recent years. Sono-photodynamic therapy (SPDT), which is an important method applied in combination with PDT and SDT, has started to be preferred in terms of reducing potential side effects compared to monotherapy. One of the most important types of sensitizers used in PDT and SDT is known as phthalocyanines (Pcs). Motivated by these facts, this research presents the sono-photochemical, in vitro cytotoxicity, and theoretical evaluation of water-soluble gallium phthalocyanine (GaPc). The results indicate that the quantum yield of the generation of singlet oxygen increased in sono-photochemical studies (ΦΔ = 0.94), compared to photochemical studies (ΦΔ = 0.72). In vitro analyses revealed that GaPc did not exhibit significant cytotoxic effects at the specified varying concentration doses (1-20 µM). Furthermore, GaPc-mediated SPDT triggered cell death by inducing reactive oxygen species formation in the breast cancer cell line (MCF-7). The interaction mechanism of the GaPc with EGFR and VEGFR2 target proteins, which are critical regulators of metastasis, proliferation, and angiogenesis, was investigated by molecular docking simulation. GaPc has effective binding affinities against target proteins, and this affinity was found to be the highest against VEGFR2. Molecular docking results showed a good correlation with the obtained biological results. Eventually, this molecular building of the efficient water-soluble phthalocyanine-based sensitizer is a potential therapeutic for PDT, SDT, and SPDT applications.

Nuclear-targeted chimeric peptide nanorods to amplify innate anti-tumor immunity through localized DNA damage and STING activation.

Stimulator of the interferon genes (STING) pathway is appealing but challenging to potentiate the innate anti-tumor immunity. In this work, nuclear-targeted chimeric peptide nanorods (designated as PFPD) are constructed to amplify innate immunity through localized DNA damage and STING activation. Among which, the chimeric peptide (PpIX-FFVLKPKKKRKV) is fabricated with photosensitizer and nucleus targeting peptide sequence, which can self-assemble into nanorods and load STING agonist of DMXAA. The uniform nanosize distribution and good stability of PFPD improve the sequential targeting delivery of drugs towards tumor cells and nuclei. Under light irradiation, PFPD produce a large amount of reactive oxygen species (ROS) to destroy nuclear DNA in situ, and the released cytosolic DNA fragment will efficiently activate innate anti-tumor immunity in combination with STING agonist. In vitro and in vivo results indicate the superior ability of PFPD to activate natural killer cells and T cells, thus efficiently eradicating lung metastatic tumor without inducing unwanted side effects. This work provides a sophisticated strategy for localized activation of innate immunity for systemic tumor treatment, which may inspire the rational design of nanomedicine for tumor precision therapy.

PEGylated chitosan-coated nanophotosensitizers for effective cancer treatment by photothermal-photodynamic therapy combined with glutathione depletion.

The combination of photothermal therapy (PTT) and photodynamic therapy (PDT) has emerged as a promising strategy for cancer treatment. However, the poor photostability and photothermal conversion efficiency (PCE) of organic small-molecule photosensitizers, and the intracellular glutathione (GSH)-mediated singlet oxygen scavenging largely decline the antitumor efficacy of PTT and PDT. Herein, a versatile nanophotosensitizer (NPS) system is developed by ingenious incorporation of indocyanine green (ICG) into the PEGylated chitosan (PEG-CS)-coated polydopamine (PDA) nanoparticles via multiple π-π stacking, hydrophobic and electrostatic interactions. The PEG-CS-covered NPS showed prominent colloidal and photothermal stability as well as high PCE (ca 62.8 %). Meanwhile, the Michael addition between NPS and GSH can consume GSH, thus reducing the GSH-induced singlet oxygen scavenging. After being internalized by CT26 cells, the NPS under near-infrared laser irradiation produced massive singlet oxygen with the aid of thermo-enhanced intracellular GSH depletion to elicit mitochondrial damage and lipid peroxide formation, thus leading to ferroptosis and apoptosis. Importantly, the combined PTT and PDT delivered by NPS effectively inhibited CT26 tumor growth in vivo by light-activated intense hyperthermia and redox homeostasis disturbance. Overall, this work presents a new tactic of boosting antitumor potency of ICG-mediated phototherapy by PEG-CS-covered NPS.

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.

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.

The fusion of light and immunity: Advancements in photoimmunotherapy for melanoma.

Metastatic melanoma is an aggressive skin cancer with high mortality and recurrence rates. Despite the clinical success of recent immunotherapy approaches, prevailing resistance rates necessitate the continued development of novel therapeutic options. Photoimmunotherapy (PIT) is emerging as a promising immunotherapy strategy that uses photodynamic therapy (PDT) to unleash systemic immune responses against tumor sites while maintaining the superior tumor-specificity and minimally invasive nature of traditional PDT. In this review, we discuss recent advances in PIT and strategies for the management of melanoma using PIT. PIT can strongly induce immunogenic cell death, inviting the concomitant application of immune checkpoint blockade or adoptive cell therapies. PIT can also be leveraged to selectively remove the suppressive immune populations associated with immunotherapy resistance. The modular nature of PIT therapy design combined with the potential for patient-specific antigen selection or drug co-delivery makes PIT an alluring option for future personalized melanoma care.

Highly Efficient Photodynamic Hydrogel with AIE-Active Photosensitizers toward Methicillin-Resistant Staphylococcus aureus Ultrafast Imaging and Killing.

Methicillin-resistant Staphylococcus aureus (MRSA) causes great health hazards to society because most antibiotics are ineffective. Photodynamic treatment (PDT) has been proposed to combat MRSA due to the advantage of imaging-guided no-drug resistance therapy. However, the traditional photosensitizers for PDT are limited by aggregation-caused quenching for imaging and low photodynamic antibacterial efficiency. In this work, we synthesize a new aggregation-induced emission (AIE) photosensitizer (APNO), which can ultrafast distinguish between Gram-positive and Gram-negative bacteria within 3 s by AIE-active photosensitizer imaging. Meanwhile, APNO can generate antibacterial reactive oxygen species under light irradiation, which holds potential for antibacterial PDT. Then, APNO is loaded by PHEAA hydrogel to obtain a highly efficient photodynamic hydrogel (APNO@gel). In vitro results show complete inhibition of MRSA by APNO@gel under lower-power light irradiation. Transcriptome analysis is performed to investigate antibacterial mechanism of APNO@gel. Most importantly, APNO@gel also exhibits significant inhibition and killing ability of MRSA in the MRSA wound infection model, which will further promote rapid wound healing. Therefore, the photodynamic hydrogel provides a promising strategy toward MRSA ultrafast imaging and killing.

The contradictory role of febuxostat in ABCG2 expression and potentiating hypericin-mediated photodynamic therapy in colorectal cancers.

Photodynamic Therapy (PDT) is an emerging method to treat colorectal cancers (CRC). Hypericin (HYP) is an effective mediator of PDT and the ABCG2 inhibitor, Febuxostat (FBX) could augment PDT. HT29 and HEK293 cells showed light dependant cytotoxic response to PDT in both 2D and 3D cell models. FBX co-treatment was not found to improve PDT cytotoxicity. Next, ABCG2 protein expression was observed in HT29 but not in HEK293 cells. However, ABCG2 gene expression analysis did not support protein expression results as ABCG2 gene expression results were found to be higher in HEK293 cells. Although HYP treatment was found to significantly reduce ABCG2 gene expression levels in both cell lines, FBX treatment partially restored ABCG2 gene expression. Our findings indicate that FBX co-treatment may not be suitable for augmenting HYP-mediated PDT in CRC but could potentially be useful for other applications.

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.