ABSTRACT
Due to antimicrobial drug resistance, there is a growing interest in the development of light based alternative antibacterial therapies. This research work is focused on the inactivation of Escherichia coli (E. coli) by exploiting the absorption bands 405, 505, 542, 580 and 631 nm of its indigenously produced Protoporphyrin IX (PpIX) excited by three LEDs with broad emission bands at 418, 522 and 630 nm and two laser diodes with narrow emission bands at 405 and 635 nm. Fluorescence spectroscopy and plate count method have been employed for studying the inactivation rate of E. coli strain in autoclaved water suspension. It has been found that LEDs at 418, 522 and 630 nm produced pronounced antimicrobial photodynamic effect on E. coli strain comparing laser diodes at 405 and 635 nm, which might be attributed to the overlapping of broad emission bands of LEDs with the absorption bands of PpIX than narrow emission bands of laser diodes. Particular effect of LED at 522 nm has been noticed because its broad emission band overlaps three absorption bands 505, 542 and 580 nm of PpIX. The gold standard plate count method strongly correlates with Fluorescence spectroscopy, making it an innovative tool to administer bacterial inactivation. The experimental results suggested the development of a light source that entirely overlap absorption bands of PpIx to produce a pronounced antimicrobial photodynamic effect, which might become an effective modality for in vivo disinfection of antibiotic resistant microbes in wounds and lesions.
Subject(s)
Escherichia coli , Photochemotherapy , Photosensitizing Agents , Protoporphyrins , Spectrometry, Fluorescence , Escherichia coli/drug effects , Photochemotherapy/methods , Photosensitizing Agents/pharmacology , Lasers, Semiconductor/therapeutic use , HumansABSTRACT
PURPOSE: The aim of this study is to describe the anatomical and functional changes observed in multiparametric magnetic resonance imaging (mpMRI) during follow-up after focal therapy (FT) for localized prostate cancer (PCa). MATERIALS AND METHODS: In this prospective study, we analyzed pre- and postoperatively acquired mpMRI of 10 patients after FT (7 days; 3, 6, 9, 12 months). 7/10 (70%) patients underwent vascular-targeted photodynamic therapy (VTP). 3/10 (30%) patients underwent high-intensity focused ultrasound (HIFU). MpMR image analysis was performed using a semi-automatic software for segmentation of the prostate gland (PG) and tumor zones. Signal intensities (SI) of T2-weighted (T2w), T1-weighted (T1w),diffusion-weighted (DWI) and dynamic contrast-enhanced (DCE) images as well as volumes of the prostate gland (PGV) and tumor volumes (TV) were evaluated at each time point. RESULTS: The results showed a significant increase of PGV 7 days after FT (p = 0.042) and a significant reduction of PGV between 7 days and 6, 9 and 12 months after FT (p < 0.001). The TV increased significantly 7 days after FT (p < 0.001) and decreased significantly between 7 days and 12 months after FT (p < 0.001). There was a significant increase in SI of the ADC in the ablation zone after 6, 9 and 12 months after FT (p < 0.001). 1/9 patients (11%) had recurrent tumor on rebiopsy characterized as a a small focal lesion on mpMRI with strong diffusion restriction (low SI on ADC map and high SI on b-value DWI). CONCLUSION: MpMRI is able to represent morphologic changes of the ablated zone after FT and might be helpful to detect recurrent tumor.
Subject(s)
Multiparametric Magnetic Resonance Imaging , Photochemotherapy , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Prostatic Neoplasms/therapy , Prostatic Neoplasms/drug therapy , Photochemotherapy/methods , Prospective Studies , Aged , Middle Aged , Photosensitizing Agents/therapeutic use , Combined Modality Therapy , Ultrasound, High-Intensity Focused, Transrectal/methods , Prostate/diagnostic imaging , Prostate/pathology , High-Intensity Focused Ultrasound Ablation/methods , Bacteriochlorophylls/therapeutic useABSTRACT
Nanotechnology-based cancer treatment has received considerable attention, and these treatments generally use drug-loaded nanoparticles (NPs) to target and destroy cancer cells. Nanotechnology combined with photodynamic therapy (PDT) has demonstrated positive outcomes in cancer therapy. Combining nanotechnology and PDT is effective in targeting metastatic cancer cells. Nanotechnology can also increase the effectiveness of PDT by targeting cells at a molecular level. Dendrimer-based nanoconjugates (DBNs) are highly stable and biocompatible, making them suitable for drug delivery applications. Moreover, the hyperbranched structures in DBNs have the capacity to load hydrophobic compounds, such as photosensitizers (PSs) and chemotherapy drugs, and deliver them efficiently to tumour cells. This review primarily focuses on DBNs and their potential applications in cancer treatment. We discuss the chemical design, mechanism of action, and targeting efficiency of DBNs in tumour metastasis, intracellular trafficking in cancer treatment, and DBNs' biocompatibility, biodegradability and clearance properties. Overall, this study will provide the most recent insights into the application of DBNs and PDT in cancer therapy.
DBNs' intracellular journey in cancer-PDT refines targeted therapy, boosting efficacy.DBN in PDT for tumour metastasis: targeting and drug release mechanisms.DBNs' biocompatibility, biodegradability and clearance were explored thoroughly.
Subject(s)
Dendrimers , Nanoconjugates , Neoplasms , Photochemotherapy , Humans , Dendrimers/chemistry , Neoplasms/drug therapy , Neoplasms/pathology , Neoplasms/metabolism , Nanoconjugates/chemistry , Nanoconjugates/therapeutic use , Animals , Photosensitizing Agents/chemistry , Photosensitizing Agents/therapeutic use , Photosensitizing Agents/pharmacology , Biological Transport , Intracellular Space/metabolism , Intracellular Space/drug effects , Drug Carriers/chemistryABSTRACT
Over the years immunotherapy has demonstrably improved the field of cancer treatment. However, achieving long-term survival for colorectal cancer (CRC) patients remains a significant unmet need. Combination immunotherapies incorporating targeted drugs like MEK or multi-kinase inhibitors have offered some palliative benefit. Nevertheless, substantial gaps remain in the current therapeutic armamentarium for CRC. In recent years, there has been a surge of interest in exploring novel treatment strategies, including the application of light-activated drugs in conjunction with optical devices. This approach holds promise for achieving localized and targeted delivery of cytotoxic agents, such as microtubule-targeting drugs, directly to cancerous cells within the colon.
Subject(s)
Colorectal Neoplasms , Microtubules , Humans , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Colorectal Neoplasms/therapy , Colorectal Neoplasms/immunology , Microtubules/drug effects , Microtubules/metabolism , Antineoplastic Agents/therapeutic use , Molecular Targeted Therapy/methods , Drug Delivery Systems/methods , Photosensitizing Agents/therapeutic use , Immunotherapy/methods , Photochemotherapy/methods , Tubulin Modulators/therapeutic use , Tubulin Modulators/pharmacologyABSTRACT
In female Wistar rats with breast cancer, quantitative changes of pro-oncogenic miRNAs (miR-21, -27a, and -221) and tumor-suppressive miR-429 in the mesenteric lymph node were assessed after photodynamic therapy for breast cancer and after photodynamic therapy followed surgical treatment. The level of pro-oncogenic miR-221 in the mesenteric lymph node decreased, and the level of pro-oncogenic miR-21 increased after photodynamic therapy for breast cancer followed by surgical treatment in comparison with the corresponding parameters after photodynamic therapy alone. The content of tumor-suppressive miR-429 remained reduced, as in the group of animals receiving photodynamic therapy alone.
Subject(s)
Lymph Nodes , MicroRNAs , Photochemotherapy , Rats, Wistar , Animals , Female , MicroRNAs/genetics , MicroRNAs/metabolism , Lymph Nodes/pathology , Lymph Nodes/drug effects , Lymph Nodes/metabolism , Photochemotherapy/methods , Rats , Mammary Neoplasms, Experimental/drug therapy , Mammary Neoplasms, Experimental/pathology , Mammary Neoplasms, Experimental/genetics , Mammary Neoplasms, Experimental/metabolism , Mesentery/pathology , Photosensitizing Agents/therapeutic use , Photosensitizing Agents/pharmacology , Gene Expression Regulation, Neoplastic/drug effects , Breast Neoplasms/pathology , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Lymphatic MetastasisABSTRACT
The antitumor performance of PROteolysis-TArgeting Chimeras (PROTACs) is limited by its insufficient tumor specificity and poor pharmacokinetics. These disadvantages are further compounded by tumor heterogeneity, especially the presence of cancer stem-like cells, which drive tumor growth and relapse. Herein, we design a region-confined PROTAC nanoplatform that integrates both reactive oxygen species (ROS)-activatable and hypoxia-responsive PROTAC prodrugs for the precise manipulation of bromodomain and extraterminal protein 4 expression and tumor eradication. These PROTAC nanoparticles selectively accumulate within and penetrate deep into tumors via response to matrix metalloproteinase-2. Photoactivity is then reactivated in response to the acidic intracellular milieu and the PROTAC is discharged due to the ROS generated via photodynamic therapy specifically within the normoxic microenvironment. Moreover, the latent hypoxia-responsive PROTAC prodrug is restored in hypoxic cancer stem-like cells overexpressing nitroreductase. Here, we show the ability of region-confined PROTAC nanoplatform to effectively degrade BRD4 in both normoxic and hypoxic environments, markedly hindering tumor progression in breast and head-neck tumor models.
Subject(s)
Cell Cycle Proteins , Nanoparticles , Proteolysis , Transcription Factors , Humans , Proteolysis/drug effects , Animals , Nanoparticles/chemistry , Cell Line, Tumor , Mice , Transcription Factors/metabolism , Female , Cell Cycle Proteins/metabolism , Reactive Oxygen Species/metabolism , Prodrugs/pharmacology , Prodrugs/chemistry , Photochemotherapy/methods , Neoplastic Stem Cells/drug effects , Neoplastic Stem Cells/metabolism , Mice, Nude , Xenograft Model Antitumor Assays , Tumor Microenvironment/drug effects , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Nuclear Proteins/metabolism , Matrix Metalloproteinase 2/metabolism , Mice, Inbred BALB C , Neoplasms/drug therapy , Neoplasms/metabolism , Neoplasms/pathology , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Bromodomain Containing ProteinsABSTRACT
PURPOSE: To evaluate the effect of MB-PDT assisted essential therapy on angle resorption of lower anterior alveolar bone in patients with periodontitis. METHODS: Forty patients who were diagnosed with periodontitis stage III-IV or C, lower anterior teeth alveolar bone angle resorption, and periodontal pocket depth greater than 4 mm were selected from April 2018 to October 2020 in the Department of Periodontology and Oral Mucosal Diseases, Changsha Stomatological Hospital. The patients were randomly divided into control group and experimental group with 20 cases in each group. Compared with the control group which was only managed with essential treatment, the experimental group was treated with MB-PDT on the basis of the control group. The plaque index (PLI) and gingival bleeding index (GBI) scores of the two groups were recorded before surgery and 1 and 2 weeks after surgery. Probing depth (PD) and clinical attachment level (CAL) were detected before and 6 months after surgery. Statistical analysis of the data was performed using Graphpad Prism 5 software package. RESULTS: The PLI and GBI of the experimental group were significantly lower than those of the control group at 1 and 2 weeks after operation(Pï¼0.05). Six months after surgery, PD and CAL levels in the experimental group were significantly lower than those in the control group (Pï¼0.05). CONCLUSIONS: MB-PDT adjuvant therapy has the advantages of simple operation, efficient sterilization, promotion of healing, and high safety performance. It may be a new non-surgical adjuvant treatment strategy for effective treatment of lower anterior alveolar angular resorption.
Subject(s)
Alveolar Bone Loss , Dental Plaque Index , Periodontal Index , Humans , Alveolar Bone Loss/therapy , Alveolar Bone Loss/drug therapy , Photochemotherapy/methods , Periodontitis/drug therapy , Periodontitis/therapy , Mandible/drug effectsABSTRACT
Photodynamic therapy (PDT), a noninvasive cancer treatment, relies on three components: light source, oxygen, and photosensitizer (PS). When PS is excited by a specific wavelength of light in the presence of oxygen, it leads to the generation of reactive oxygen species (ROS), which results in targeted destruction of cancer cells. The success of PDT mainly depends on the properties of the chosen PS, emphasizing selectivity, high absorbance, drug conjugation, controlled biodistribution, and low toxicity. Nanomaterials not only play an important role in photochemical activity by maximizing the absorption of photons from the light source but can also adjust the pharmacokinetics and tumor selectivity of photoactive molecules. Therefore, they can be used as a PS on their own and conjugated with other PS molecules. When combined with selectivity, high targeting capacity, and finally, light of the appropriate wavelength, the scenario results in localized ROS formation and cell death. However, the signaling pathways of PDT-induced cell death may differ depending on the cell type or nanomaterial properties. For this reason, omics analyses are needed to clarify the mechanisms underlying photodynamic reactions. Proteomics, crucial in molecular sciences, sheds light on cancer mechanisms, identifying biomarkers and therapeutic targets. Examining nanoparticle-based PDT in cancer cell lines in vitro, this chapter aims to molecularly evaluate efficacy, utilizing proteomic analysis to understand the underlying mechanisms.
Subject(s)
Nanostructures , Neoplasms , Photochemotherapy , Photosensitizing Agents , Reactive Oxygen Species , Photochemotherapy/methods , Humans , Neoplasms/drug therapy , Neoplasms/metabolism , Photosensitizing Agents/therapeutic use , Photosensitizing Agents/pharmacology , Reactive Oxygen Species/metabolism , Nanostructures/chemistry , Cell Line, Tumor , Proteomics/methods , Nanoparticles/chemistryABSTRACT
SIGNIFICANCE: Multilesional basal cell carcinoma (BCC) are spread on sun exposed skin areas, including arms, face and back. The first-line treatment remains the surgical resection or Mohs surgery. Despite its high complexity, Mohs surgery is well practiced in USA and Germany and presents very good results both in esthetic and in carcinology point of view. Large lesions more than 2 cm remain challenging to remove by topical cream used in photodynamic therapy (PDT). If these larger lesions are not treated in less than 1 month, they could grow deeply in the skin, thus enhancing the risk of reoccurrence and the severity of the disease. Despite this model herein studied, that is non melanoma skin cancer is a good prognostic cancer, the therapy aims to be applied to more aggressive melanoma skin cancers. AIM: Total regression of large cutaneous lesions less than 1 month with no reoccurrence. APPROACH: Tumor induction on murine model bearing a 500 mm3 subcutaneous lesion. Increasing dose of gold nanoparticles at fixed initial concentration C0 = 0.3 mg/mL, infused into the tumor then exposition of the region of interest to NIR medical laser to assess the therapy. One or two intratumoral administration(s) were compared to surgery and control, that is no treatment, laser alone or nanoparticles alone. RESULTS: Gold nanoparticles alone or the NIR laser alone did not induce the tumor regression. The combination of laser and nanoparticles called plasmonic nanophotothermal therapy induced apoptosis. Derma and hypoderm do not show any visible gold nanoparticles and demonstrated a good cicatrization process. CONCLUSION: Plasmonic nanophotothermal therapy using two doses of gold nanoparticles was the only protocol that proved its efficacy on large lesions in 14 days, that is 500 mm3 on a murine model bearing human basal cell carcinoma.
Subject(s)
Carcinoma, Basal Cell , Gold , Metal Nanoparticles , Photothermal Therapy , Skin Neoplasms , Carcinoma, Basal Cell/pathology , Carcinoma, Basal Cell/therapy , Gold/chemistry , Animals , Skin Neoplasms/pathology , Skin Neoplasms/therapy , Metal Nanoparticles/therapeutic use , Humans , Mice , Photothermal Therapy/methods , Cell Line, Tumor , Photochemotherapy/methods , Female , Combined Modality Therapy/methodsABSTRACT
Photothermal, photodynamic and sonodynamic cancer therapies offer opportunities for precise tumor ablation and reduce side effects. The cyclic guanylate adenylate synthase-stimulator of interferon genes (cGAS-STING) pathway has been considered a potential target to stimulate the immune system in patients and achieve a sustained immune response. Combining photothermal, photodynamic and sonodynamic therapies with cGAS-STING agonists represents a newly developed cancer treatment demonstrating noticeable innovation in its impact on the immune system. Recent reviews have concentrated on diverse materials and their function in cancer therapy. In this review, we focus on the molecular mechanism of photothermal, photodynamic and sonodynamic cancer therapies and the connected role of cGAS-STING agonists in treating cancer.
Subject(s)
Membrane Proteins , Neoplasms , Nucleotidyltransferases , Photochemotherapy , Humans , Neoplasms/therapy , Neoplasms/drug therapy , Neoplasms/metabolism , Nucleotidyltransferases/metabolism , Membrane Proteins/metabolism , Photochemotherapy/methods , Signal Transduction/drug effects , Animals , Ultrasonic Therapy/methods , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Photosensitizing Agents/chemistryABSTRACT
Since the molecular mechanisms behind adaptation and the bacterial stress response toward antimicrobial photodynamic therapy (aPDT) are not entirely clear yet, the aim of the present study was to investigate the transcriptomic stress response in Escherichia coli after sublethal treatment with aPDT using RNA sequencing (RNA-Seq). Planktonic cultures of stationary phase E. coli were treated with aPDT using a sublethal dose of the photosensitizer SAPYR. After treatment, RNA was extracted, and RNA-Seq was performed on the Illumina NextSeq 500. Differentially expressed genes were analyzed and validated by qRT-PCR. Furthermore, expression of specific stress response proteins was investigated using Western blot analysis.The analysis of the differential gene expression following pathway enrichment analysis revealed a considerable number of genes and pathways significantly up- or down-regulated in E. coli after sublethal treatment with aPDT. Expression of 1018 genes was up-regulated and of 648 genes was down-regulated after sublethal treatment with aPDT as compared to irradiated controls. Analysis of differentially expressed genes and significantly de-regulated pathways showed regulation of genes involved in oxidative stress response and bacterial membrane damage. In conclusion, the results show a transcriptomic stress response in E. coli upon exposure to aPDT using SAPYR and give an insight into potential molecular mechanisms that may result in development of adaptation.
Subject(s)
Escherichia coli , Photochemotherapy , Photosensitizing Agents , Escherichia coli/drug effects , Photosensitizing Agents/pharmacology , RNA-Seq , Anti-Bacterial Agents/pharmacology , Stress, Physiological/drug effectsABSTRACT
Graphene Quantum Dots (GQDs) have shown the potential for antimicrobial photodynamic treatment, due to their particular physicochemical properties. Here, we investigated the activity of three differently functionalized GQDs-Blue Luminescent GQDs (L-GQDs), Aminated GQDs (NH2-GQDs), and Carboxylated GQDs (COOH-GQDs)-against E. coli. GQDs were administrated to bacterial suspensions that were treated with blue light. Antibacterial activity was evaluated by measuring colony forming units (CFUs) and metabolic activities, as well as reactive oxygen species stimulation (ROS). GQD cytotoxicity was then assessed on human colorectal adenocarcinoma cells (Caco-2), before setting in an in vitro infection model. Each GQD exhibits antibacterial activity inducing ROS and impairing bacterial metabolism without significantly affecting cell morphology. GQD activity was dependent on time of exposure to blue light. Finally, GQDs were able to reduce E. coli burden in infected Caco-2 cells, acting not only in the extracellular milieu but perturbating the eukaryotic cell membrane, enhancing antibiotic internalization. Our findings demonstrate that GQDs combined with blue light stimulation, due to photodynamic properties, have a promising antibacterial activity against E. coli. Nevertheless, we explored their action mechanism and toxicity on epithelial cells, fixing and standardizing these infection models.
Subject(s)
Anti-Bacterial Agents , Blue Light , Escherichia coli , Graphite , Quantum Dots , Reactive Oxygen Species , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Caco-2 Cells , Escherichia coli/drug effects , Graphite/chemistry , Graphite/pharmacology , Photochemotherapy/methods , Quantum Dots/chemistry , Reactive Oxygen Species/metabolismABSTRACT
Over the past decades, medicine has made enormous progress, revolutionized by modern technologies and innovative therapeutic approaches. One of the most exciting branches of these developments is photodynamic therapy (PDT). Using a combination of light of a specific wavelength and specially designed photosensitizing substances, PDT offers new perspectives in the fight against cancer, bacterial infections, and other diseases that are resistant to traditional treatment methods. In today's world, where there is a growing problem of drug resistance, the search for alternative therapies is becoming more and more urgent. Imagine that we could destroy cancer cells or bacteria using light, without the need to use strong chemicals or antibiotics. This is what PDT promises. By activating photosensitizers using appropriately adjusted light, this therapy can induce the death of cancer or bacterial cells while minimizing damage to surrounding healthy tissues. In this work, we will explore this fascinating method, discovering its mechanisms of action, clinical applications, and development prospects. We will also analyze the latest research and patient testimonies to understand the potential of PDT for the future of medicine.
Subject(s)
Neoplasms , Photochemotherapy , Photosensitizing Agents , Photochemotherapy/methods , Humans , Photosensitizing Agents/therapeutic use , Neoplasms/drug therapy , Animals , Bacterial Infections/drug therapyABSTRACT
The spread of multidrug-resistant mycobacterium strains requires the development of new approaches to combat diseases caused by these pathogens. For that, photodynamic inactivation (PDI) is a promising approach. In this study, a tricarbocyanine (TCC) is used for the first time as a near-infrared (740 nm) activatable PDI photosensitizer to kill mycobacteria with deep light penetration. For better targeting, a novel tricarbocyanine dye functionalized with two trehalose units (TCC2Tre) is developed. The photodynamic effect of the conjugates against mycobacteria, including Mycobacterium tuberculosis, is evaluated. Under irradiation, TCC2Tre causes more effective killing of mycobacteria compared to the photosensitizer without trehalose conjugation, with 99.99% dead vegetative cells of M. tuberculosis and M. smegmatis. In addition, effective photoinactivation of dormant forms of M. smegmatis is observed after incubation with TCC2Tre. Mycobacteria treated with TCC2Tre are more sensitive to 740 nm light than the Gram-positive Micrococcus luteus and the Gram-negative Escherichia coli. For the first time, this study demonstrates the proof of principle of in vitro PDI of mycobacteria including the fast-growing M. smegmatis and the slow-growing M. tuberculosis using near-infrared activatable photosensitizers conjugated with trehalose. These findings are useful for the development of new efficient alternatives to antibiotic therapy.
Subject(s)
Infrared Rays , Mycobacterium smegmatis , Mycobacterium tuberculosis , Photosensitizing Agents , Trehalose , Mycobacterium smegmatis/drug effects , Mycobacterium smegmatis/radiation effects , Trehalose/pharmacology , Trehalose/chemistry , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/radiation effects , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemistry , Carbocyanines/chemistry , Carbocyanines/pharmacology , Photochemotherapy/methodsABSTRACT
OBJECTIVE: Chronic wounds are costly and difficult to treat, resulting in morbidity and even mortality in some cases due to a high methicillin-resistant Staphylococcus aureus (MRSA) burden contributing to chronicity. We aimed to observe the antimicrobial activity and healing-promoting effect of a novel photosensitizer Shengtaibufen (STBF)-mediated antibacterial photodynamic therapy (PDT) on MRSA-infected chronic leg ulcers. PATIENTS AND METHODS: This was a retrospective, comparative, single-center clinical study. A total of 32 patients with chronic lower limb wounds infected with MRSA from January 2022 to December 2023 were finally included in this study by searching the electronic medical records of the dermatology department of Huadong Hospital, including a group of red light combined with iodophor (control+iodophor, n=16, receiving red light once a week for 8 weeks and routine dressing change with iodophor once a day) and a group of STBF-mediated PDT (STBF-PDT) combined with iodophor (STBF-PDT+iodophor, n=16, receiving STBF-PDT and routine dressing change with iodophor once a day). STBF-PDT was performed once a week (1 mg/ml STBF, 1 h incubation, 630 nm red light, 80 J/cm2) for 8 weeks. The primary endpoints included wound clinical signs, wound size, wound-related pain, re-epithelialization score, MRSA load and wound-related quality of life (wound-QoL). Any adverse events were also recorded. RESULTS: We found that STBF-PDT+iodophor could effectively alleviate clinical infection symptoms, accelerate wound closure, reduce average biological burden and improve wound-QoL without severe adverse events in comparison to the control+iodophor group. The STBF-PDT+iodophor group obtained a mean percentage reduction of 65.22% in wound size (from 18.96±11.18 cm2 to 6.59±7.94 cm2) and excellent re-epithelialization scores, as compared with a decrease of 30.17% (from 19.23±9.80 cm2 to 13.43±9.32 cm2) for the control+iodophor group. Significant differences in wound area were observed at week 6 (p=0.028*) and week 8 (p=0.002**). The bacterial load decreased by 99.86% (from 6.45 × 107±2.69 × 107 to 8.94 × 104±1.92 × 105 CFU/cm2, p<0.0001) in the STBF-PDT+iodophor group and 1.82% (from 6.61 × 107±2.13 × 107 to 6.49 × 107±2.01 × 107 CFU/cm2, p=0.029) in the control+iodophor group. The wound-QoL in STBF-PDT+iodophor group had a 51.62% decrease in overall score (from 29.65±9.33 at the initial to 14.34±5.17 at week 8, p<0.0001) compared to those receiving red light and routine wound care (from 30.73±17.16 to 29.32±15.89 at week 8, p=0.003). Moreover, patients undergoing STBF-PDT+iodophor exhibited great improvements in all domains of wound-QoL (physical, psychological and everyday-life), whereas the control+iodophor group ameliorated in only one field (everyday-life). CONCLUSION: Our data confirmed that a novel photosensitizer, STBF-mediated PDT, when combined with iodophor, served as a potential modality for MRSA infection and a possible therapy for other drug-resistant microorganisms, and as a promising alternative for chronic cutaneous infectious diseases.
Subject(s)
Iodophors , Methicillin-Resistant Staphylococcus aureus , Photochemotherapy , Photosensitizing Agents , Humans , Photochemotherapy/methods , Methicillin-Resistant Staphylococcus aureus/drug effects , Retrospective Studies , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Male , Female , Aged , Middle Aged , Iodophors/pharmacology , Leg Ulcer/drug therapy , Leg Ulcer/microbiology , Wound Healing/drug effects , Chronic Disease , Staphylococcal Infections/drug therapy , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Aged, 80 and over , Porphyrins/pharmacology , Porphyrins/therapeutic useABSTRACT
Naphthalocyanine-based agents exhibit huge potential in photodynamic therapy, yet their photodynamic performance is restricted by the penetration depth of the external laser. Herein, we employed 18F-FDG as an internal light source to excite silicon naphthalocyanine nanoparticles to simultaneously circumvent radiative transition and boost 1O2 generation for tumor suppression.
Subject(s)
Nanoparticles , Photochemotherapy , Photosensitizing Agents , Nanoparticles/chemistry , Humans , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemical synthesis , Animals , Radiopharmaceuticals/chemistry , Radiopharmaceuticals/pharmacology , Mice , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Neoplasms/drug therapy , Neoplasms/diagnostic imaging , Singlet Oxygen/metabolism , Singlet Oxygen/chemistry , Silicon/chemistryABSTRACT
5-Aminolevulinic acid (5-ALA) is a prodrug of porphyrin IX (PpIX). Disadvantages of 5-ALA include poor stability, rapid elimination, poor bioavailability, and weak cell penetration, which greatly reduce the clinical effect of 5-ALA based photodynamic therapy (PDT). Presently, a novel targeting nanosystem was constructed using gold nanoparticles (AuNPs) as carriers loaded with a CSNIDARAC (CC9)-targeting peptide and 5-ALA via Au-sulphur and ionic bonds, respectively, and then wrapped in polylactic glycolic acid (PLGA) NPs via self-assembly to improve the antitumor effects and reduce the side effect. The successful preparation of ALA/CC9@ AuNPs-PLGA NPs was verified using ultraviolet-visible, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. The analyses revealed good sphericity with a particle size of approximately140 nm, Zeta potential of 10.11 mV, and slow-controlled release characteristic in a weak acid environment. Confocal microscopy revealed targeting of NCL-H460 cells by NPs by actively internalising CC9 and avoiding the phagocytic action of RAW264.7 cells, and live fluorescence imaging revealed targeting of tumours in tumour-bearing mice. Compared to free 5-ALA, the nanosystem displayed amplified anticancer activity by increasing production of PpIX and reactive oxygen species to induce mitochondrial pathway apoptosis. Antitumor efficacy was consistently observed in three-dimensionally cultured cells as the loss of integrity of tumour balls. More potent anti-tumour efficacy was demonstrated in xenograft tumour models by decreased growth rate and increased tumour apoptosis. Histological analysis showed that this system was not toxic, with lowered liver toxicity of 5-ALA. Thus, ALA/CC9@AuNPs-PLGA NPs deliver 5-ALA via a carrier cascade, with excellent effects on tumour accumulation and PDT through passive enhanced permeability and retention action and active targeting. This innovative strategy for cancer therapy requires more clinical trials before being implemented.
Subject(s)
Aminolevulinic Acid , Gold , Lung Neoplasms , Metal Nanoparticles , Photochemotherapy , Aminolevulinic Acid/chemistry , Aminolevulinic Acid/pharmacology , Aminolevulinic Acid/therapeutic use , Animals , Gold/chemistry , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Lung Neoplasms/metabolism , Mice , Metal Nanoparticles/chemistry , Metal Nanoparticles/therapeutic use , Cell Line, Tumor , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Reactive Oxygen Species/metabolism , Drug Carriers/chemistry , Apoptosis/drug effects , Lactic Acid/chemistry , Polyglycolic Acid/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic useABSTRACT
BACKGROUND: Photodynamic therapy (PDT) is a pioneering and effective anticancer modality with low adverse effects and high selectivity. Hypochlorous acid or hypochlorite (HClO/ClO-) is a type of inflammatory cytokine. The abnormal increase of ClO- in tumor cells is related to tumor pathogenesis and may be a "friend" for the design and synthesis of responsive phototherapy agents. However, preparing responsive phototherapy agents for all-in-one noninvasive diagnosis and simultaneous in situ therapy in a complex tumor environment is highly desirable but still remains an enormously demanding task. RESULTS: An acceptor-π bridge-donor-π bridge-acceptor (A-π-D-π-A) type photosensitizer TPTPy was designed and synthesized based on the phenothiazine structure which was used as the donor moiety as well as a ClO- responsive group. TPTPy was a multifunctional mitochondria targeted aggregation-induced emission (AIE) photosensitizer which could quickly and sensitively respond to ClO- with fluorescence "turn on" performance (19-fold fluorescence enhancement) and enhanced type I reactive oxygen species (ROS) generation to effectively ablate hypoxic tumor cells. The detection limit of TPTPy to ClO- was calculated to be 185.38 nM. The well-tailored TPTPy anchoring to mitochondria and producing ROS in situ could disrupt mitochondria and promote cell apoptosis. TPTPy was able to image inflammatory cells and tumor cells through ClO- response. In vivo results revealed that TPTPy was successfully utilized for PDT in tumor bearing nude mice and exhibited excellent biological safety for major organs. SIGNIFICANCE AND NOVELTY: A win-win integration strategy was proposed to design a tumor intracellular ClO- responsive photosensitizer TPTPy capable of both type I and type II ROS production to achieve photodynamic therapy of tumor. This work sheds light on the win-win integration design by taking full advantage of the characteristics of tumor microenvironment to build up responsive photosensitizer for in situ PDT of tumor.
Subject(s)
Hypochlorous Acid , Mitochondria , Photochemotherapy , Photosensitizing Agents , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemical synthesis , Photosensitizing Agents/therapeutic use , Hypochlorous Acid/analysis , Hypochlorous Acid/metabolism , Animals , Humans , Mitochondria/drug effects , Mitochondria/metabolism , Mice , Reactive Oxygen Species/metabolism , Reactive Oxygen Species/analysis , Mice, Inbred BALB C , Phenothiazines/chemistry , Phenothiazines/pharmacology , Mice, Nude , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Optical Imaging , Cell Survival/drug effectsABSTRACT
This network meta-analysis aims to compare the clinical efficacy of seven non-surgical therapies for peri-implant disease, including laser treatment, photobiomodulation therapy (PBMT), photodynamic therapy (PDT), systemic antibiotics (SA), probiotics, local antimicrobials (LA), and air-powder polishing (APP) combined with mechanical debridement (MD). We conducted searches in four electronic databases, namely PubMed, Embase, Web of Science, and The Cochrane Library, to identify randomized controlled trials of non-surgical treatments combined with MD for individuals (aged at least 18 years) diagnosed with peri-implantitis or peri-implant mucositis with a minimum of 3 months follow-up. The outcomes of the study were the reduction in pocket probing depth (PPD) and bleeding on probing (BoP), plaque index (PLI), clinical attachment level (CAL), and marginal bone loss (MBL). We employed a frequency random effects network meta-analysis model to combine the effect sizes of the trials using standardized mean difference (SMD) and 95% confidence intervals (CIs). Network meta-analyses include network plots, paired comparison forest plots, league tables, funnel plots, surface under the cumulative ranking area (SUCRA) plots, and sensitivity analysis plots. The results showed that, for peri-implantitis, PBMT +MD demonstrated the highest effect in improving PPD (SUCRA = 75.3%), SA +MD showed the highest effect in improving CAL (SUCRA = 87.4%, SMD = 2.20, and 95% CI: 0.38 to 4.02) and MBL (SUCRA = 99.9%, SMD = 3.92, and 95% CI. 2.90 to 4.93), compared to MD alone. For peri-implant mucositis, probiotics +MD demonstrated the highest effect in improving PPD (SUCRA = 100%) and PLI (SUCRA = 83.2%), SA +MD showed the highest effect in improving BoP (SUCRA = 88.1%, SMD = 0.77, and 95% CI: 0.27 to 1.28), compared to MD alone. Despite the ranking established by our study in the treatment of peri-implant disease, decisions should still be made with reference to the latest treatment guidelines. There is still a need for more high-quality studies to provide conclusive evidence and especially a need for studies regarding direct comparisons between multiple treatment options.
Subject(s)
Debridement , Peri-Implantitis , Humans , Peri-Implantitis/therapy , Debridement/methods , Network Meta-Analysis , Treatment Outcome , Photochemotherapy/methods , Probiotics/therapeutic use , Anti-Bacterial Agents/therapeutic use , Dental Implants/adverse effects , Stomatitis/therapy , Stomatitis/radiotherapy , Stomatitis/etiology , Mucositis/therapy , Laser Therapy/methodsABSTRACT
Nanomaterials with photoresponsivity have garnered attention due to their fluorescence imaging, photodynamic, and photothermal therapeutic properties. In this study, a photoresponsivity nanoassembly was developed by using photosensitizers and carbon dots (CDs). Due to their multiple excitation peaks and multicolor fluorescence emission, especially their membrane-permeating properties, these nanoassemblies can label cells with multiple colors and track cell imaging in real time. Additionally, the incorporation of photosensitizers and CDs provides the nanoassemblies with the potential for photodynamic therapy (PDT) and photothermal therapy (PTT). The nanoassemblies effectively suppressed the activity of Escherichia coli and Staphylococcus aureus through PDT and PTT. Moreover, the nanoassemblies exhibited a high affinity for E. coli and S. aureus. These distinct features confer broad-spectrum antibacterial properties to the nanoassemblies. As a photoresponsivity nanoplatform, these nanoassemblies have demonstrated potential applications in the fields of bioimaging and antimicrobial.