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International Journal of Pharmaceutics Jun 2024Because of the difficult challenges of nanopharmaceutics, the development of a variety of nanovectors is still highly desired. Photodynamic therapy, which uses a...
Because of the difficult challenges of nanopharmaceutics, the development of a variety of nanovectors is still highly desired. Photodynamic therapy, which uses a photosensitizer to locally produce reactive oxygen species to kill the undesired cells, is a typical example for which encapsulation has been shown to be beneficial. The present work describes the use of coumarin-functionalized polymeric nanovectors based on the self-assembly of amphiphilic poly(2-oxazoline)s. Encapsulation of pheophorbide a, a known PDT photosensitizer, is shown to lead to an increased efficiency compared to the un-encapsulated version. Interestingly, the presence of coumarin both enhances the desired photocytotoxicity and enables the crosslinking of the vectors. Various nanovectors are examined, differing by their size, shape and hydrophilicity. Their behaviour in PDT protocols on HCT-116 cells monolayers is described, the influence of their crosslinking commented. Furthermore, the formation of a protein corona is assessed.
Topics: Photochemotherapy; Humans; Coumarins; Oxazoles; Photosensitizing Agents; HCT116 Cells; Cell Survival; Chlorophyll; Nanoparticles; Drug Carriers; Polymers
PubMed: 38701908
DOI: 10.1016/j.ijpharm.2024.124186 -
International Journal of Nanomedicine 2024Chemo-photodynamic combination therapy has demonstrated significant potential in the treatment of cancer. Triptolide (TPL), a naturally derived anticancer agent,...
BACKGROUND
Chemo-photodynamic combination therapy has demonstrated significant potential in the treatment of cancer. Triptolide (TPL), a naturally derived anticancer agent, when combined with the photosensitizer Chlorin e6 (Ce6), has shown to provide enhanced anti-tumor benefits. However, the development of stimuli-responsive nanovehicles for the co-delivery of TPL and Ce6 could further enhance the efficacy of this combination therapy.
METHODS
In this study, we synthesized a pH/ROS dual-responsive mPEG--PBAE copolymer, which contains a pH-sensitive PBAE moiety and a ROS-sensitive thioketal (TK) linkage. Through a self-assembly process, TPL and Ce6 were successfully co-loaded into mPEG--PBAE nanoparticles, hereafter referred to as TPL/Ce6 NPs. We evaluated the pH- and ROS-sensitive drug release and particle size changes. Furthermore, we investigated both the in vitro suppression of cellular proliferation and induction of apoptosis in HepG2 cells, as well as the in vivo anti-tumor efficacy of TPL/Ce6 NPs in H22 xenograft nude mice.
RESULTS
The mPEG--PBAE copolymer was synthesized through a one-pot Michael-addition reaction and successfully co-encapsulated both TPL and Ce6 by self-assembly. Upon exposure to acid pH values and high ROS levels, the payloads in TPL/Ce6 NPs were rapidly released. Notably, the abundant ROS generated by the released Ce6 under laser irradiation further accelerated the degradation of the nanosystem, thereby amplifying the tumor microenvironment-responsive drug release and enhancing anticancer efficacy. Consequently, TPL/Ce6 NPs significantly increased PDT-induced oxidative stress and augmented TPL-induced apoptosis in HepG2 cells, leading to synergistic anticancer effects in vitro. Moreover, administering TPL/Ce6 NPs (containing 0.3 mg/kg of TPL and 4 mg/kg of Ce6) seven times, accompanied by 650 nm laser irradiation, efficiently inhibited tumor growth in H22 tumor-bearing mice, while exhibiting lower systemic toxicity.
CONCLUSION
Overall, we have developed a tumor microenvironment-responsive nanosystem for the co-delivery of TPL and Ce6, demonstrating amplified synergistic effects of chemo-photodynamic therapy (chemo-PDT) for hepatocellular carcinoma (HCC) treatment.
Topics: Animals; Humans; Chlorophyllides; Photochemotherapy; Reactive Oxygen Species; Hep G2 Cells; Liver Neoplasms; Porphyrins; Diterpenes; Hydrogen-Ion Concentration; Photosensitizing Agents; Mice, Nude; Apoptosis; Mice; Carcinoma, Hepatocellular; Epoxy Compounds; Nanoparticles; Xenograft Model Antitumor Assays; Antineoplastic Agents; Drug Liberation; Cell Proliferation; Polyethylene Glycols; Combined Modality Therapy; Phenanthrenes
PubMed: 38699684
DOI: 10.2147/IJN.S453199 -
BMC Ophthalmology May 2024We aimed to employ Optical Coherence Tomography Angiography (OCTA) to comprehensively assess changes in the optic nerve head (ONH) and macular perfusion before and after...
BACKGROUND
We aimed to employ Optical Coherence Tomography Angiography (OCTA) to comprehensively assess changes in the optic nerve head (ONH) and macular perfusion before and after the Corneal Collagen Cross-Linking (CCL) procedure in patients with keratoconus.
METHODS
A total of 22 keratoconus patient's candidate for CCL procedures were included based on specific criteria, with meticulous exclusion criteria in place to minimize potential confounders. Participants underwent OCTA assessments of the ONH and macula using the Spectralis OCT (Heidelberg) before CCL, as well as at 1- and 3-months post-CCL. MATLAB software was utilized for image analysis.
RESULTS
The mean age of the participants was 20.09 ± 6.11, including 59% male, and the mean intraocular pressure (IOP) before the surgery was 13.59 ± 2.85 mmHg. Peripapillary Retinal nerve fiber layer (ppRNFL) thickness and overall retinal thickness remained stable post-CCL. However, significant alterations were observed in macular vessel density, emphasizing regional variations in vascular response. For macular large vessel density (LVD), both superficial and deep vascular complex (SVC and DVC) demonstrated significant differences between before surgery and the 3 months post-surgery follow-up (p < 0.001 and p = 0.002, respectively). Optic nerve head markers demonstrated relative stability, except for changes in avascular complex density, which was 49.2 ± 2.2% before the surgery and decrease to 47.6 ± 1.7% three months after the operation (P-value = 0.005).
CONCLUSION
While CCL appears to maintain the integrity of certain ocular structures, alterations in macular perfusion post-CCL suggest potential effects on retinal blood supply. Long-term monitoring is crucial to understand the implications of these changes, particularly in the context of conditions such as diabetes.
Topics: Humans; Tomography, Optical Coherence; Keratoconus; Male; Female; Collagen; Young Adult; Adult; Fluorescein Angiography; Retinal Vessels; Optic Disk; Cross-Linking Reagents; Adolescent; Prospective Studies; Photosensitizing Agents; Photochemotherapy; Macula Lutea
PubMed: 38698363
DOI: 10.1186/s12886-024-03470-1 -
Photodiagnosis and Photodynamic Therapy Jun 2024To assess the impact of various cavity disinfectants PC-PDT (Phycocyanin activated by Photodynamic therapy), PC@AgNPs-PDT (Phycocyanin and silver nanoparticles activated...
Phycocyanin-loaded silver nanoparticles activated with photodynamic therapy and Nd: YAG laser for caries-affected dentin disinfection: Impact on Streptococcus mutans survival rate and shear bond strength to the tooth-colored restorative material.
To assess the impact of various cavity disinfectants PC-PDT (Phycocyanin activated by Photodynamic therapy), PC@AgNPs-PDT (Phycocyanin and silver nanoparticles activated by PDT), and Nd: YAG laser on the survival rate of S.mutans and the bond integrity of composite restoration METHODS: Sixty human mandibular molars that scored 4 and 5 based on ICDAS criteria were included. The infected dentin was removed while the CAD was preserved based on visual, tactile, and staining assessment. S.mutans were cultured on the CAD of twenty samples. All the specimens were indiscriminately distributed into four groups based on cavity disinfection (n=20 each includes n = 5 each group incubated with S.mutans) Group 1: CHX, Group 2: Nd:YAG laser, Group 3: PC-PDT and Group 4: PC@AgNPs-PDT. S.mutans survival rate was assessed for each group(n = 5). Forty samples underwent composite bonding for SBS and failure mode assessment using universal testing machine (UTM) and stereomicroscope. The calculations for the mean and standard deviation (SD) and their comparison among different groups were performed using a one-way analysis of variance (ANOVA) and the Tukey post hoc test (p ≤ 0.05) RESULTS: CAD surface treated disinfected with PC@AgNPs-PDT yielded the lowest survival rates (0.13 ± 0.05 CFU/ml) and highest SBS (17.23 ± 1.45 MPa). Group 1 (CHX) unveiled the highest survival rate of S.mutans (0.33 ± 0.12 CFU/ml). However, Group 2 (Nd:YAG Laser) (11.87 ± 0.67 MPa) presented the lowest SBS CONCLUSION: The combination of Phycocyanin loaded with silver nanoparticles and activated with Photodynamic therapy demonstrates the highest antimicrobial potential and bond strength of composite restorations.
Topics: Photochemotherapy; Silver; Humans; Streptococcus mutans; Metal Nanoparticles; Phycocyanin; Photosensitizing Agents; Lasers, Solid-State; Dental Caries; Dentin; Disinfection; Shear Strength; Molar
PubMed: 38697450
DOI: 10.1016/j.pdpdt.2024.104108 -
Journal of Applied Oral Science :... 2024To evaluate whether antimicrobial photodynamic therapy (aPDT) repairs bisphosphonate-related osteonecrosis of the jaw (BRONJ) modulated by the reduction of NF-kB protein...
OBJECTIVE
To evaluate whether antimicrobial photodynamic therapy (aPDT) repairs bisphosphonate-related osteonecrosis of the jaw (BRONJ) modulated by the reduction of NF-kB protein in a murine model.
METHODOLOGY
Male Wistar rats (N=30) were divided into the following groups (n=6/group): negative control (NC); experimental osteonecrosis (ONE); ONE + photosensitizer (PS); ONE + photobiomodulation (PBM); and ONE + aPDT. Over 8 weeks, ONE was induced by zoledronic acid 250 µg/kg injections, except in the NC group, which received sterile 0.9% saline, followed by extraction of the lower left first molar. Red light laser irradiation (wavelength ~660 nm, power 50 mW, energy of 2 J, energy dose of 66.67 J/cm2 for 40 s) was performed once a week for 4 weeks. Methylene blue 0.3% was used as PS. The animals were euthanized and examined macroscopically for the presence of exposed bone and epithelial repair and microscopically by histochemical (hematoxylin-eosin and Masson's trichrome staining) and immunohistochemical (anti-NF-kB) methods. Macroscopic and histomorphometric data were analyzed by one-way ANOVA and Tukey's post-test (p<0.05).
RESULTS
Mucosal repair, viable osteocytes, and NF-kB immunostaining were observed in the NC, ONE+PS, ONE+PBM, and ONE+aPDT groups. The ONE group showed no mucosal repair, showing empty lacunae and multifocal immunostaining for NF-kB. The ONE+PBM and ONE+aPDT groups had greater deposition of extracellular matrix and less necrotic bone tissue (p<0.05).
CONCLUSION
PBM and aPDT treatments for BRONJ were effective for bone and epithelial repair, in addition to reducing inflammation mediated by the decrease of NF-kB protein in the irradiated regions.
Topics: Animals; Rats, Wistar; Male; Photochemotherapy; Bisphosphonate-Associated Osteonecrosis of the Jaw; NF-kappa B; Photosensitizing Agents; Immunohistochemistry; Disease Models, Animal; Time Factors; Reproducibility of Results; Zoledronic Acid; Treatment Outcome; Imidazoles; Diphosphonates; Low-Level Light Therapy; Methylene Blue; Analysis of Variance; Random Allocation; Bone Density Conservation Agents
PubMed: 38695448
DOI: 10.1590/1678-7757-2023-0447 -
Scientific Reports May 2024A series of 4-carboxyphenyl/4-hydroxyphenyl meso-substituted porphyrins were synthesized, purified, and characterized. The compounds exhibited anti-HIV-1 activities, in...
A series of 4-carboxyphenyl/4-hydroxyphenyl meso-substituted porphyrins were synthesized, purified, and characterized. The compounds exhibited anti-HIV-1 activities, in vitro, under both non-photodynamic (non-PDT) and photodynamic (PDT) conditions. Specifically, the porphyrins inhibited HIV-1 virus entry, with c-PB(OH) and PB(OH) showing significant anti-HIV-1 activity. All of the porphyrins inhibited HIV-1 subtype B and C virus entry under PDT conditions. Our study demonstrated that the compounds bearing combinations of 4-carboxyphenyl/4-hydroxyphenyl moieties were not toxic even at higher concentrations, as compared to the reference porphyrins 5,10,15,20-tetra-(4-carboxyphenyl)porphyrin (TCPP) and 5,10,15,20-tetra-(4-hydroxyphenyl)porphyrin (THPP), under PDT conditions. This study underscores the promising potential of these compounds as HIV entry inhibitors in both non-PDT and PDT scenarios.
Topics: Porphyrins; HIV-1; Anti-HIV Agents; Humans; Virus Internalization; HIV Infections; Photochemotherapy
PubMed: 38693160
DOI: 10.1038/s41598-024-60728-w -
Journal of Nanobiotechnology Apr 2024The main issues faced during the treatment of apical periodontitis are the management of bacterial infection and the facilitation of the repair of alveolar bone defects...
BACKGROUND
The main issues faced during the treatment of apical periodontitis are the management of bacterial infection and the facilitation of the repair of alveolar bone defects to shorten disease duration. Conventional root canal irrigants are limited in their efficacy and are associated with several side effects. This study introduces a synergistic therapy based on nitric oxide (NO) and antimicrobial photodynamic therapy (aPDT) for the treatment of apical periodontitis.
RESULTS
This research developed a multifunctional nanoparticle, CGP, utilizing guanidinylated poly (ethylene glycol)-poly (ε-Caprolactone) polymer as a carrier, internally loaded with the photosensitizer chlorin e6. During root canal irrigation, the guanidino groups on the surface of CGP enabled effective biofilm penetration. These groups undergo oxidation by hydrogen peroxide in the aPDT process, triggering the release of NO without hindering the production of singlet oxygen. The generated NO significantly enhanced the antimicrobial capability and biofilm eradication efficacy of aPDT. Furthermore, CGP not only outperforms conventional aPDT in eradicating biofilms but also effectively promotes the repair of alveolar bone defects post-eradication. Importantly, our findings reveal that CGP exhibits significantly higher biosafety compared to sodium hypochlorite, alongside superior therapeutic efficacy in a rat model of apical periodontitis.
CONCLUSIONS
This study demonstrates that CGP, an effective root irrigation system based on aPDT and NO, has a promising application in root canal therapy.
Topics: Animals; Photochemotherapy; Nitric Oxide; Biofilms; Rats; Nanoparticles; Photosensitizing Agents; Periapical Periodontitis; Male; Root Canal Irrigants; Rats, Sprague-Dawley; Bacterial Infections; Chlorophyllides; Anti-Bacterial Agents; Anti-Infective Agents
PubMed: 38689259
DOI: 10.1186/s12951-024-02483-8 -
ACS Applied Materials & Interfaces May 2024Of the most common, hypoxia, overexpressed glutathione (GSH), and insufficient HO concentration in the tumor microenvironment (TME) are the main barriers to the...
Of the most common, hypoxia, overexpressed glutathione (GSH), and insufficient HO concentration in the tumor microenvironment (TME) are the main barriers to the advancment of reactive oxygen species (ROS) mediated Xdynamic therapies (X = photo, chemodynamic, chemo). Maximizing Fenton catalytic efficiency is crucial in chemodynamic therapy (CDT), yet endogenous HO levels are not sufficient to attain better anticancer efficacy. Specifically, there is a need to amplify Fenton reactivity within tumors, leveraging the unique attributes of the TME. Herein, for the first time, we design RuCuO-Ce6/CPT (RCpCCPT) anticancer nanoagent for TME-mediated synergistic therapy based on heterogeneous Ru-Cu peroxide nanodots (RuCuO NDs) and chlorine e6 (Ce6), loaded with ROS-responsive thioketal (TK) linked-camptothecin (CPT). The Ru-Cu peroxide NDs (RCp NDs, = 0.50) possess the highest oxygen vacancy (O) density, which grants them the potential to form massive Lewis's acid sites for peroxide adsorption, while the dispersibility and targetability of the NDs were improved via surface modification using hyaluronic acid (HA). In TME, RCpCCPT degrades, releasing HO, Ru, and Cu ions, which cooperatively facilitate hydroxyl radical (•OH) formation and deactivate antioxidant GSH enzymes through a cocatalytic loop, resulting in excellent tumor therapeutic efficacy. Furthermore, when combined with laser treatment, RCpCCPT produces singlet oxygen (O) for PDT, which induces cell apoptosis at tumor sites. Following ROS generation, the TK linkage is disrupted, releasing up to 92% of the CPT within 48 h. In vitro investigations showed that laser-treated RCpCCPT caused 81.5% cell death from PDT/CDT and chemotherapy (CT). RCpCCPT in cancer cells produces red-blue emission in images of cells taking them in, which allows for fluorescence image-guided Xdynamic treatment. The overall results show that RCp NDs and RCpCCPT are more biocompatible and have excellent Xdynamic therapeutic effectiveness in vitro and in vivo.
Topics: Hydrogen Peroxide; Tumor Microenvironment; Copper; Animals; Mice; Humans; Ruthenium; Nanoparticles; Antineoplastic Agents; Peroxides; Cell Line, Tumor; Photochemotherapy; Drug Carriers; Reactive Oxygen Species; Neoplasms
PubMed: 38688027
DOI: 10.1021/acsami.3c18888 -
Oncology Research 2024Photodynamic therapy (PDT) is a promising cancer treatment. This study investigated the antitumor effects and mechanisms of a novel photosensitizer meso-5-[ρ-diethylene...
Photodynamic therapy (PDT) is a promising cancer treatment. This study investigated the antitumor effects and mechanisms of a novel photosensitizer meso-5-[ρ-diethylene triamine pentaacetic acid-aminophenyl]-10,15,20-triphenyl-porphyrin (DTP) mediated PDT (DTP-PDT). Cell viability, reactive oxygen species (ROS), and apoptosis were measured with a Cell Counting Kit-8 assay, DCFH-DA fluorescent probe, and Hoechst staining, respectively. Cell apoptosis- and autophagy-related proteins were examined using western blotting. RNA sequencing was used to screen differentially expressed mRNAs (DERs), and bioinformatic analysis was performed to identify the major biological events after DTP-PDT. Our results show that DTP-PDT inhibited cell growth and induced ROS generation in MCF-7 and SGC7901 cells. The ROS scavenger N-acetyl-L-cysteine (NAC) and the P38 MAPK inhibitor SB203580 alleviated DTP-PDT-induced cytotoxicity. DTP-PDT induced cell apoptosis together with upregulated Bax and downregulated Bcl-2, which could also be inhibited by NAC or SB203580. The level of LC3B-II, a marker of autophagy, was increased by DTP-PDT. A total of 3496 DERs were obtained after DTP-PDT. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that DERs included those involved in cytosolic ribosomes, the nuclear lumen, protein binding, cell cycle, protein targeting to the endoplasmic reticulum, and ribosomal DNA replication. Disease Ontology and Reactome enrichment analyses indicated that DERs were associated with a variety of cancers and cell cycle checkpoints. Protein-protein interaction results demonstrated that and ranked in the top 10 interacting genes. Therefore, DTP-PDT could inhibit cell growth and induce cell apoptosis and autophagy, partly through ROS and the P38 MAPK signaling pathway. Genes associated with the cell cycle, ribosomes, DNA replication, and protein binding may be the key changes in DTP-PDT-mediated cytotoxicity.
Topics: Humans; Photochemotherapy; Photosensitizing Agents; Reactive Oxygen Species; Transcriptome; Apoptosis; Cell Line, Tumor; Porphyrins; Cell Proliferation; Cell Survival; Autophagy; MCF-7 Cells; Gene Expression Regulation, Neoplastic; Neoplasms; Gene Expression Profiling
PubMed: 38686054
DOI: 10.32604/or.2023.042384 -
Photodiagnosis and Photodynamic Therapy Jun 2024Both the traditional loop electrosurgical excision procedure (LEEP) and the newly developed 5-aminolevulinic acid photodynamic therapy (ALA-PDT) are used to treat... (Comparative Study)
Comparative Study
BACKGROUND
Both the traditional loop electrosurgical excision procedure (LEEP) and the newly developed 5-aminolevulinic acid photodynamic therapy (ALA-PDT) are used to treat high-grade squamous intraepithelial lesions. However, the clinical efficacy and safety of these two therapies have rarely been compared. Thus, this study aimed to compare the clinical efficacy and safety of the two treatment regimens.
METHODS
One hundred and twenty patients in two groups (60 + 60) with grade 2 cervical intraepithelial neoplasia (CIN2) were voluntary treated with photodynamic therapy or LEEP between June 2020 and December 2022. Follow-up was conducted at 3, 4-6, and 7-12 months after treatment.
RESULTS
Although the total effective rate of LEEP was higher during the first 6 months after treatment, both the total effective rate of lesion degradation and the double-negative rate of high-risk HPV16/18 and liquid-based cervical cytology by ALA-PDT treatment increased with time and finally exceeded those of LEEP at 7-12 months.
CONCLUSIONS
ALA-PDT may be more promising than LEEP for treating patients with CIN2 because of the better CIN2 degradation and high-risk HPV negativity, less damage, and greater fertility conservation, especially after 6 months.
Topics: Humans; Aminolevulinic Acid; Female; Photochemotherapy; Photosensitizing Agents; Uterine Cervical Dysplasia; Electrosurgery; Adult; Middle Aged; Uterine Cervical Neoplasms
PubMed: 38685549
DOI: 10.1016/j.pdpdt.2024.104107