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Journal of Biological Inorganic... Apr 2024This study demonstrates the potential of sono-photodynamic therapy as an effective approach for enhancing singlet oxygen generation using the synthesized Schiff-base...
Monitoring of singlet oxygen generation of a novel Schiff-base substituted silicon phthalocyanines by sono-photochemical studies and in vitro activities on prostate cancer cell.
This study demonstrates the potential of sono-photodynamic therapy as an effective approach for enhancing singlet oxygen generation using the synthesized Schiff-base diaxially substituted silicon phthalocyanines. In photochemical studies, the singlet oxygen quantum yields (Φ) were determined as 0.43 for Si1a, 0.94 for Q-Si1a, 0.58 for S-Si1a, and 0.49 for B-Sia1. In sono-photochemical studies, the Φ values were reached to 0.67 for Si1a, 1.06 for Q-Si1a, 0.65 for S-Si1a, and 0.67 for B-Sia1. In addition, this study demonstrates the therapeutic efficacy of phthalocyanines synthesized as sensitizers on the PC3 prostate cancer cell line through in vitro experiments. The application of these treatment modalities exhibited notable outcomes, leading to a substantial decrease in cell viability within the PC3 prostate cancer cell line. These findings highlight the potential of utilizing these synthesized phthalocyanines as promising therapeutic agents for prostate cancer treatment.
Topics: Humans; Indoles; Schiff Bases; Male; Singlet Oxygen; Prostatic Neoplasms; Organosilicon Compounds; Cell Survival; Photosensitizing Agents; Antineoplastic Agents; Drug Screening Assays, Antitumor; PC-3 Cells; Photochemotherapy; Photochemical Processes; Cell Line, Tumor; Molecular Structure
PubMed: 38727821
DOI: 10.1007/s00775-024-02055-z -
Photodiagnosis and Photodynamic Therapy Jun 2024Photodynamic therapy (PDT) is used for the treatment of centrally-located early lung cancers (CLELCs) and is recommended for tumors ≤ 1.0 cm in diameter. We previously...
BACKGROUND
Photodynamic therapy (PDT) is used for the treatment of centrally-located early lung cancers (CLELCs) and is recommended for tumors ≤ 1.0 cm in diameter. We previously reported that PDT using talaporfin sodium, second-generation photosensitizer, for tumors > 1.0 cm but ≤ 2.0 cm in diameter was able to achieve a therapeutic outcome comparable to that of tumors with a diameter of ≤ 1.0 cm. However, the effectiveness of PDT using talaporfin sodium for tumors > 2.0 cm in diameter remains unclear. We conducted a retrospective analysis of cases in which PDT was performed for flat-type CLELCs with tumor diameters of > 2.0 cm.
METHODS
We retrospectively analyzed seven cases (eight lesions) with tumor diameters > 2.0 cm and no evidence of extracartilaginous invasion or lymph node metastasis.
RESULTS
All the patients underwent multiple PDT sessions. The PDT treatment results over the study period were partial response in one case (14.3 %), stable disease (SD) in three cases (42.9 %), and progressive disease (PD) in three cases (42.9 %). At the time of writing this report, five of seven cases (71.4 %) are still undergoing treatment. The duration of SD-the time from the start of treatment until the criteria for PD were met (SD or better maintained)-ranged from 7 to 52 months (mean, 25.3 months).
CONCLUSIONS
"Maintenance PDT" for CLELCs > 2.0 cm in diameter has the potential to inhibit tumor progression in the long term while maintaining quality of life, rather than simply aiming only for a quick radical cure.
Topics: Humans; Photochemotherapy; Lung Neoplasms; Photosensitizing Agents; Male; Aged; Female; Retrospective Studies; Middle Aged; Porphyrins; Aged, 80 and over; Treatment Outcome
PubMed: 38723757
DOI: 10.1016/j.pdpdt.2024.104200 -
International Journal of Nanomedicine 2024Graphene and graphene-based materials have attracted growing interest for potential applications in medicine because of their good biocompatibility, cargo capability and... (Review)
Review
Graphene and graphene-based materials have attracted growing interest for potential applications in medicine because of their good biocompatibility, cargo capability and possible surface functionalizations. In parallel, prototypic graphene-based devices have been developed to diagnose, imaging and track tumor growth in cancer patients. There is a growing number of reports on the use of graphene and its functionalized derivatives in the design of innovative drugs delivery systems, photothermal and photodynamic cancer therapy, and as a platform to combine multiple therapies. The aim of this review is to introduce the latest scientific achievements in the field of innovative composite graphene materials as potentially applied in cancer therapy. The "Technology and Innovation Roadmap" published in the Graphene Flagship indicates, that the first anti-cancer drugs using graphene and graphene-derived materials will have appeared on the market by 2030. However, it is necessary to broaden understanding of graphene-based material interactions with cellular metabolism and signaling at the functional level, as well as toxicity. The main aspects of further research should elucidate how treatment methods (e.g., photothermal therapy, photodynamic therapy, combination therapy) and the physicochemical properties of graphene materials influence their ability to modulate autophagy and kill cancer cells. Interestingly, recent scientific reports also prove that graphene nanocomposites modulate cancer cell death by inducing precise autophagy dysfunctions caused by lysosome damage. It turns out as well that developing photothermal oncological treatments, it should be taken into account that near-infrared-II radiation (1000-1500 nm) is a better option than NIR-I (750-1000 nm) because it can penetrate deeper into tissues due to less scattering at longer wavelengths radiation.
Topics: Graphite; Humans; Antineoplastic Agents; Neoplasms; Drug Delivery Systems; Photochemotherapy; Autophagy; Animals; Nanocomposites; Nanomedicine
PubMed: 38711615
DOI: 10.2147/IJN.S447397 -
Journal of Nanobiotechnology May 2024Elevated interstitial fluid pressure within tumors, resulting from impaired lymphatic drainage, constitutes a critical barrier to effective drug penetration and...
BACKGROUND
Elevated interstitial fluid pressure within tumors, resulting from impaired lymphatic drainage, constitutes a critical barrier to effective drug penetration and therapeutic outcomes.
RESULTS
In this study, based on the photosynthetic characteristics of algae, an active drug carrier (CP@ICG) derived from Chlorella pyrenoidosa (CP) was designed and constructed. Leveraging the hypoxia tropism and phototropism exhibited by CP, we achieved targeted transport of the carrier to tumor sites. Additionally, dual near-infrared (NIR) irradiation at the tumor site facilitated photosynthesis in CP, enabling the breakdown of excessive intratumoral interstitial fluid by generating oxygen from water decomposition. This process effectively reduced the interstitial pressure, thereby promoting enhanced perfusion of blood into the tumor, significantly improving deep-seated penetration of chemotherapeutic agents, and alleviating tumor hypoxia.
CONCLUSIONS
CP@ICG demonstrated a combined effect of photothermal/photodynamic/starvation therapy, exhibiting excellent in vitro/in vivo anti-tumor efficacy and favorable biocompatibility. This work provides a scientific foundation for the application of microbial-enhanced intratumoral drug delivery and tumor therapy.
Topics: Animals; Photosynthesis; Mice; Cell Line, Tumor; Chlorella; Drug Carriers; Humans; Combined Modality Therapy; Photochemotherapy; Neoplasms; Antineoplastic Agents; Mice, Inbred BALB C; Drug Delivery Systems; Indocyanine Green; Female
PubMed: 38711078
DOI: 10.1186/s12951-024-02476-7 -
Photodiagnosis and Photodynamic Therapy Jun 2024Hemoporfin-mediated photodynamic therapy (HMME-PDT) has been recognized as a safe and effective treatment for port wine stain (PWS). However, some patients show limited...
SIGNIFICANCE
Hemoporfin-mediated photodynamic therapy (HMME-PDT) has been recognized as a safe and effective treatment for port wine stain (PWS). However, some patients show limited improvement even after multiple treatments. Herein, we aim to explore the effect of autophagy on HMME-PDT in human umbilical vein endothelial cells (HUVECs), so as to provide theoretical basis and treatment strategies to enhance clinical effectiveness.
METHODS
Establish the in vitro HMME-PDT system by HUVECs. Apoptosis and necrosis were identified by Annexin Ⅴ-FITC/PI flow cytometry, and autophagy flux was detected by monitoring RFP-GFP-LC3 under the fluorescence microscope. Hydroxychloroquine and rapamycin were employed in the mechanism study. Specifically, the certain genes and proteins were qualified by qPCR and Western Blot, respectively. The cytotoxicity was measured by CCK-8, VEGF-A secretion was determined by ELISA, and the tube formation of HUVECs was observed by angiogenesis assay.
RESULTS
In vitro experiments revealed that autophagy and apoptosis coexisted in HUVECs treated by HMME-PDT. Apoptosis was dominant in early stage, while autophagy gradually increased in the middle and late stage. AMPK, AKT and mTOR participated in the regulation of autophagy induced by HMME-PDT, in which AMPK was positive regulation, while AKT and mTOR were negative regulation. Hydroxychloroquine could not inhibit HMME-PDT-induced autophagy, but capable of blocking the fusion of autophagosomes with lysosome. Rapamycin might cooperate with HMME-PDT to enhance autophagy in HUVECs, leading to increased cytotoxicity, reduced VEGF-A secretion, and weakened angiogenesis ability.
CONCLUSIONS
Both autophagy and apoptosis contribute to HMME-PDT-induced HUVECs death. Pretreatment of HUVECs with rapamycin to induce autophagy might enhance the photodynamic killing effect of HMME-PDT on HUVECs. The combination of Rapamycin and HMME-PDT is expected to further improve the clinical efficacy.
Topics: Humans; Human Umbilical Vein Endothelial Cells; Photochemotherapy; Autophagy; Photosensitizing Agents; Apoptosis; Sirolimus; Hydroxychloroquine; Porphyrins; Vascular Endothelial Growth Factor A
PubMed: 38710260
DOI: 10.1016/j.pdpdt.2024.104196 -
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