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Photodiagnosis and Photodynamic Therapy Jun 2024To determine the long-term efficacy and safety of 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) for treating cervical intraepithelial neoplasia grade 2...
BACKGROUND
To determine the long-term efficacy and safety of 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) for treating cervical intraepithelial neoplasia grade 2 (CIN2) as well as the suitability of ALA-PDT in treating of cervical lesions divided into cervical transformation zone type 3.
METHODS
We included 81 patients diagnosed with CIN2 at the Department of Gynecology of the Affiliated Hospital of Qingdao University with data collected between January 2019 and January 2021 following ALA-PDT. Furthermore, we analyzed the superiority of ALA-PDT in fertility preservation among women of childbearing age based on follow-up data from 11 patients with fertility requirements.
RESULTS
Our findings confirmed the long-term efficacy of ALA-PDT for CIN2 treatment, with an overall efficacy of 95.83 % (23/24) at follow-up of 25-36 months. Moreover, the cervical transformation zone type 3 improvement and human papillomavirus (HPV)-negative efficacy were 69.2 % (18/26) and 82.4 % (14/17), respectively. ALA-PDT is recommended for consenting patients with cervical transformation zone type 3. Additionally, women without primary infertility could experience natural pregnancy and full-term birth of more than one baby following ALA-PDT for CIN2 treatment, with a satisfaction rate of ≈100 %.
CONCLUSIONS
ALA-PDT is recommendable for treating high-grade squamous intraepithelial lesions, especially in patients with fertility requirements.
Topics: Humans; Female; Photochemotherapy; Aminolevulinic Acid; Uterine Cervical Dysplasia; Photosensitizing Agents; Adult; Follow-Up Studies; Uterine Cervical Neoplasms; Middle Aged; Young Adult
PubMed: 38768844
DOI: 10.1016/j.pdpdt.2024.104219 -
International Journal of Nanomedicine 2024Photodynamic Therapy (PDT) is a promising, minimally invasive treatment for cancer with high immunostimulatory potential, no reported drug resistance, and reduced side...
INTRODUCTION
Photodynamic Therapy (PDT) is a promising, minimally invasive treatment for cancer with high immunostimulatory potential, no reported drug resistance, and reduced side effects. Indocyanine Green (ICG) has been used as a photosensitizer (PS) for PDT, although its poor stability and low tumor-target specificity strongly limit its efficacy. To overcome these limitations, ICG can be formulated as a tumor-targeting nanoparticle (NP).
METHODS
We nanoformulated ICG into recombinant heavy-ferritin nanocages (HFn-ICG). HFn has a specific interaction with transferrin receptor 1 (TfR1), which is overexpressed in most tumors, thus increasing HFn tumor tropism. First, we tested the properties of HFn-ICG as a PS upon irradiation with a continuous-wave diode laser. Then, we evaluated PDT efficacy in two breast cancer (BC) cell lines with different TfR1 expression levels. Finally, we measured the levels of intracellular endogenous heavy ferritin (H-Fn) after PDT treatment. In fact, it is known that cells undergoing ROS-induced autophagy, as in PDT, tend to increase their ferritin levels as a defence mechanism. By measuring intracellular H-Fn, we verified whether this interplay between internalized HFn and endogenous H-Fn could be used to maximize HFn uptake and PDT efficacy.
RESULTS
We previously demonstrated that HFn-ICG stabilized ICG molecules and increased their delivery to the target site in vitro and in vivo for fluorescence guided surgery. Here, with the aim of using HFn-ICG for PDT, we showed that HFn-ICG improved treatment efficacy in BC cells, depending on their TfR1 expression. Our data revealed that endogenous H-Fn levels were increased after PDT treatment, suggesting that this defence reaction against oxidative stress could be used to enhance HFn-ICG uptake in cells, increasing treatment efficacy.
CONCLUSION
The strong PDT efficacy and peculiar Trojan horse-like mechanism, that we revealed for the first time in literature, confirmed the promising application of HFn-ICG in PDT.
Topics: Indocyanine Green; Breast Neoplasms; Humans; Female; Photochemotherapy; Cell Line, Tumor; Receptors, Transferrin; Photosensitizing Agents; Nanoparticles; Apoferritins; Ferritins; Antigens, CD; Drug Carriers; Cell Survival; MCF-7 Cells
PubMed: 38766663
DOI: 10.2147/IJN.S445334 -
Journal of Colloid and Interface Science Sep 2024The clinical translation of photosensitizers based on ruthenium(II) polypyridyl complexes (RPCs) in photodynamic therapy of cancer faces several challenges. To address...
The clinical translation of photosensitizers based on ruthenium(II) polypyridyl complexes (RPCs) in photodynamic therapy of cancer faces several challenges. To address these limitations, we conducted an investigation to assess the potential of a cubosome formulation stabilized in water against coalescence utilizing a polyphosphoester analog of Pluronic F127 as a stabilizer and loaded with newly synthesized RPC-based photosensitizer [Ru(dppn)(bpy-morph)](PF) (bpy-morph = 2,2'-bipyridine-4,4'-diylbis(morpholinomethanone)), PS-Ru. The photophysical characterization of PS-Ru revealed its robust capacity to induce the formation of singlet oxygen (O). Furthermore, the physicochemical analysis of the PS-Ru-loaded cubosomes dispersion demonstrated that the encapsulation of the photosensitizer within the nanoparticles did not disrupt the three-dimensional arrangement of the lipid bilayer. The biological tests showed that PS-Ru-loaded cubosomes exhibited significant phototoxic activity when exposed to the light source, in stark contrast to empty cubosomes and to the same formulation without irradiation. This promising outcome suggests the potential of the formulation in overcoming the drawbacks associated with the clinical use of RPCs in photodynamic therapy for anticancer treatments.
Topics: Photochemotherapy; Photosensitizing Agents; Lung Neoplasms; Humans; Ruthenium; Coordination Complexes; Adenocarcinoma of Lung; Antineoplastic Agents; Particle Size; Singlet Oxygen; Nanoparticles; Cell Survival; Poloxamer; Drug Screening Assays, Antitumor; Surface Properties; A549 Cells
PubMed: 38761576
DOI: 10.1016/j.jcis.2024.05.088 -
Free Radical Biology & Medicine Aug 2024Photodynamic therapy is a noninvasive treatment in which specific photosensitizers and light are used to produce high amounts of reactive oxygen species (ROS), which can...
Photodynamic therapy is a noninvasive treatment in which specific photosensitizers and light are used to produce high amounts of reactive oxygen species (ROS), which can be employed for targeted tissue destruction in cancer treatment or antimicrobial therapy. However, it remains unknown whether lower amounts of ROS produced by mild photodynamic therapy increase lifespan and stress resistance at the organism level. Here, we introduce a novel photodynamic treatment (PDTr) that uses 20 μM hypericin, a photosensitizer that originates from Hypericum perforatum, and orange light (590 nm, 5.4 W/m, 1 min) to induce intracellular ROS formation (ROS), thereby resulting in lifespan extension and improved stress resistance in C. elegans. The PDTr-induced increase in longevity was abrogated by N-acetyl cysteine, suggesting the hormetic response was driven by prooxidative mechanisms. PDTr activated the translocation of SKN-1/NRF-2 and DAF-16/FOXO, leading to elevated expression of downstream oxidative stress-responsive genes, including ctl-1, gst-4, and sod-3. In summary, our findings suggest a novel PDTr method that extends the lifespan of C. elegans under both normal and oxidative stress conditions through the activation of SKN-1 and DAF-16 via the involvement of many antioxidant genes.
Topics: Animals; Caenorhabditis elegans; Oxidative Stress; Longevity; Caenorhabditis elegans Proteins; Photochemotherapy; Photosensitizing Agents; Reactive Oxygen Species; Transcription Factors; Perylene; Anthracenes; Forkhead Transcription Factors; DNA-Binding Proteins; Superoxide Dismutase; NF-E2-Related Factor 2; Gene Expression Regulation; Light; Acetylcysteine
PubMed: 38754743
DOI: 10.1016/j.freeradbiomed.2024.05.023 -
Journal of Neuro-oncology Jul 2024Glioblastoma remains incurable despite optimal multimodal management. The interim analysis of open label, single arm INDYGO pilot trial showed actuarial 12-months...
PURPOSE
Glioblastoma remains incurable despite optimal multimodal management. The interim analysis of open label, single arm INDYGO pilot trial showed actuarial 12-months progression-free survival (PFS) of 60% (median 17.1 months), actuarial 12-months overall survival (OS) of 80% (median 23.1 months). We report updated, exploratory analyses of OS, PFS, and health-related quality of life (HRQOL) for patients receiving intraoperative photodynamic therapy (PDT) with 5-aminolevulinic acid hydrochloride (5-ALA HCl).
METHODS
Ten patients were included (May 2017 - April 2021) for standardized therapeutic approach including 5-ALA HCl fluorescence-guided surgery (FGS), followed by intraoperative PDT with a single 200 J/cm dose of light. Postoperatively, patients received adjuvant therapy (Stupp protocol) then followed every 3 months (clinical and cerebral MRI) and until disease progression and/or death. Procedure safety and toxicity occurring during the first four weeks after PDT were assessed. Data concerning relapse, HRQOL and survival were prospectively collected and analyzed.
RESULTS
At the cut-off date (i.e., November 1st 2023), median follow-up was 23 months (9,7-71,4). No unacceptable or unexpected toxicities and no treatment-related deaths occurred during the study. Kaplan-Meier estimated 23.4 months median OS, actuarial 12-month PFS rate 60%, actuarial 12-month, 24-month, and 5-year OS rates 80%, 50% and 40%, respectively. Four patients were still alive (1 patient free of recurrence).
CONCLUSION
At 5 years-follow-up, intraoperative PDT with surgical maximal excision as initial therapy and standard adjuvant treatment suggests an increase of time to recurrence and overall survival in a high proportion of patients. Quality of life was maintained without any severe side effects.
TRIAL REGISTRATION NCT NUMBER
NCT03048240. EudraCT number: 2016-002706-39.
Topics: Humans; Glioblastoma; Male; Brain Neoplasms; Female; Middle Aged; Photochemotherapy; Follow-Up Studies; Aged; Aminolevulinic Acid; Photosensitizing Agents; Adult; Quality of Life; Pilot Projects; Survival Rate
PubMed: 38753093
DOI: 10.1007/s11060-024-04693-4 -
Biomacromolecules Jun 2024Two different poly(benzylmalate) biopolymers, a hydrophobic non-PEGylated () and an amphiphilic PEGylated derivative (), have been used to encapsulate a phthalocyanine...
Two different poly(benzylmalate) biopolymers, a hydrophobic non-PEGylated () and an amphiphilic PEGylated derivative (), have been used to encapsulate a phthalocyanine chosen for its substitution pattern that is highly suitable for photodynamic therapy. Different phthalocyanine/(co)polymers ratios have been used for the nanoprecipitation. A set of six nanoparticles has been obtained. If the amphiphilic PEGylated copolymer proved to be slightly more efficient for the encapsulation and to lower the aggregation of the phthalocyanine inside the nanoparticles, it is, however, the hydrophobic -based nanoparticles that exhibited the best photodynamic efficiency.
Topics: Indoles; Isoindoles; Photochemotherapy; Biopolymers; Nanoparticles; Photosensitizing Agents; Polymers; Polyethylene Glycols; Hydrophobic and Hydrophilic Interactions
PubMed: 38752976
DOI: 10.1021/acs.biomac.3c01382 -
International Journal of Nanomedicine 2024The study aimed to address the non-specific toxicity of cytotoxins (CTX) in liver cancer treatment and explore their combined application with the photosensitizer Ce6,...
PURPOSE
The study aimed to address the non-specific toxicity of cytotoxins (CTX) in liver cancer treatment and explore their combined application with the photosensitizer Ce6, co-loaded into carbonized Zn/Co bimetallic organic frameworks. The goal was to achieve controlled CTX release and synergistic photodynamic therapy, with a focus on evaluating anti-tumor activity against human liver cancer cell lines (Hep G2).
METHODS
Purified cobra cytotoxin (CTX) and photosensitizer Ce6 were co-loaded into carbonized Zn/Co bimetallic organic frameworks, resulting in RGD-PDA@C-ZIF@(CTX+Ce6). The formulation was designed with surface-functionalization using polydopamine and tumor-penetrating peptide RGD. This approach aimed to facilitate controlled CTX release and enhance the synergistic effect of photodynamic therapy. The accumulation of RGD-PDA@C-ZIF@(CTX+Ce6) at tumor sites was achieved through RGD's active targeting and the enhanced permeability and retention (EPR) effect. In the acidic tumor microenvironment, the porous structure of the metal-organic framework disintegrated, releasing CTX and Ce6 into tumor cells.
RESULTS
Experiments demonstrated that RGD-PDA@C-ZIF@(CTX+Ce6) nanoparticles, combined with near-infrared laser irradiation, exhibited optimal anti-tumor effects against human liver cancer cells. The formulation showcased heightened anti-tumor activity without discernible systemic toxicity.
CONCLUSION
The study underscores the potential of utilizing metal-organic frameworks as an efficient nanoplatform for co-loading cytotoxins and photodynamic therapy in liver cancer treatment. The developed formulation, RGD-PDA@C-ZIF@(CTX+Ce6), offers a promising avenue for advancing the clinical application of cytotoxins in oncology, providing a solid theoretical foundation for future research and development.
Topics: Humans; Photochemotherapy; Metal-Organic Frameworks; Liver Neoplasms; Zinc; Indoles; Photosensitizing Agents; Animals; Hep G2 Cells; Cobalt; Oligopeptides; Polymers; Mice; Cytotoxins; Mice, Nude; Mice, Inbred BALB C; Cell Survival
PubMed: 38751660
DOI: 10.2147/IJN.S453275 -
Acta Dermato-venereologica May 2024Photodynamic therapy is an approved treatment for primary, superficial, and small nodular basal cell carcinomas with a thickness of < 2 mm located on low-risk sites.... (Comparative Study)
Comparative Study
Photodynamic therapy is an approved treatment for primary, superficial, and small nodular basal cell carcinomas with a thickness of < 2 mm located on low-risk sites. Histologically verified basal cell carcinomas clinically assessed as suited for photodynamic therapy were included. The study aimed to investigate the agreement between clinical and histological assessments of basal cell carcinoma subtypes and thickness of tumours selected for photodynamic therapy with histopathological evaluation as a reference. A total of 343 tumours were included. The agreement between clinical and histological diagnosis of basal cell carcinoma subtype was 72% (p < 0.001). Clinical assessment of subtype had a sensitivity of 93% and specificity of 55% for superficial tumours and a sensitivity of 55% and specificity of 85% for nodular tumours. The mean ± SD thickness values by clinical and histological assessments were 0.95 ± 0.53 and 0.86 ± 0.75. The difference of 0.09 mm was statistically significant (p = 0.017), but not considered to be clinically relevant, although the differences between specific subgroups could be relevant. Among basal cell carcinomas clinically diagnosed as superficial, 91% were histologically consistent with the current photodynamic therapy criteria. The main results suggest that histopathological evaluation should precede photodynamic therapy to ensure selection of suitable basal cell carcinomas. In selected cases, the clinical diagnosis alone may be adequate before proceeding with photodynamic therapy.
Topics: Humans; Carcinoma, Basal Cell; Photochemotherapy; Skin Neoplasms; Male; Female; Aged; Middle Aged; Aged, 80 and over; Predictive Value of Tests; Biopsy; Adult; Patient Selection; Photosensitizing Agents; Retrospective Studies
PubMed: 38751175
DOI: 10.2340/actadv.v104.18308 -
Lasers in Medical Science May 2024Photodynamic therapy (PDT) is a targeted treatment method that utilizes a photosensitizer (PS) to induce cytotoxicity in malignant and non-malignant tumors. Optimization...
Photodynamic therapy (PDT) is a targeted treatment method that utilizes a photosensitizer (PS) to induce cytotoxicity in malignant and non-malignant tumors. Optimization of PDT requires investigation of the selectivity of PS for the target tissues, irradiating light source, irradiation wavelengths, fluence rate, fluence, illumination mode, and overall treatment plan. In this study, we developed the Multi-mode Automatized Well-plate PDT LED Laboratory Irradiation System (MAWPLIS), an innovative device that automates time-consuming well plate light dosage/PS dose measurement experiment. The careful control of LED current and temperature stabilization in the LED module allowed the system to achieve high optical output stability. The MAWPLIS was designed by integrating a 3-axis moving system and motion controller, a quick-switching LED controller unit equipped with interchangeable LED modules capable of employing multiple wavelengths, and a TEC system. The proposed system achieved high optical output stability (1 mW) within the range of 0-500 mW, high wavelength stability (5 nm) at 635 nm, and high temperature stability (0.2 °C) across all radiation modes. The system's validation involved in vitro analysis using 5-ALA across varying concentrations, incubation periods, light exposures, and wavelengths in HT-29 colon cancer and WI-38 human lung fibroblast cell lines. Specifically, a combination of 405 nm and 635 nm wavelengths was selected to demonstrate enhanced strategies for colon cancer cell eradication and system validation. The MAWPLIS system represents a significant advancement in photodynamic therapy (PDT) research, offering automation and standardization of time-intensive experiments, high stability and precision, and improved PDT efficacy through dual-wavelength integration.
Topics: Photochemotherapy; Humans; Photosensitizing Agents; HT29 Cells; Aminolevulinic Acid
PubMed: 38750381
DOI: 10.1007/s10103-024-04083-2 -
Chinese Medical Journal Jun 2024
Topics: Humans; Keratosis, Actinic; Aminolevulinic Acid; Photochemotherapy; Prospective Studies; Male; Female; Middle Aged; Aged; Photosensitizing Agents; East Asian People
PubMed: 38749769
DOI: 10.1097/CM9.0000000000003014