-
Journal of Inorganic Biochemistry Jul 2024This work reports on the synthesis of triphenylphosphine-labelled cationic phthalocyanines (Pc) complexed with bovine serum albumin (BSA) and gold nanoparticles (Au...
Anticancer photodynamic activities of triphenylphosphine-labelled phthalocyanines and their bovine serum albumin-gold nanoparticles- complexes on melanoma A375 cell lines in vitro.
This work reports on the synthesis of triphenylphosphine-labelled cationic phthalocyanines (Pc) complexed with bovine serum albumin (BSA) and gold nanoparticles (Au NPs). This nano-complex (Pc-BSA-Au) is studied for its photodynamic therapy (PDT) activity compared to the non-complexed Pc counterpart. The photochemical properties and in vitro PDT efficacies of the Pc and the nano-complex were determined and are compared herein. The singlet oxygen (O) yields of the Pcs were determined and are reported in DMF. A singlet oxygen quantum yield of 0.47 was obtained for the Pcs. The PDT efficacies of the complexes were thereafter determined using malignant melanoma A375 cancer cell line in vitro. An increase in the cell toxicity was observed for cells treated with Pc-BSA-Au compared to those treated with the Pc alone. The cell survival percentages were 23.1% for cells treated with Pc-BSA-Au and 48.7% for those treated with Pc alone under PDT treatments.
Topics: Gold; Serum Albumin, Bovine; Humans; Metal Nanoparticles; Photochemotherapy; Indoles; Cell Line, Tumor; Organophosphorus Compounds; Melanoma; Photosensitizing Agents; Isoindoles; Animals; Antineoplastic Agents; Cell Survival; Cattle; Singlet Oxygen
PubMed: 38685138
DOI: 10.1016/j.jinorgbio.2024.112570 -
Photodiagnosis and Photodynamic Therapy Jun 2024Cholangiocarcinoma (CCA) is a malignant tumor with a poor prognosis. The specific mechanism of photodynamic therapy (PDT) in treating CCA remains unclear. This study...
BACKGROUND
Cholangiocarcinoma (CCA) is a malignant tumor with a poor prognosis. The specific mechanism of photodynamic therapy (PDT) in treating CCA remains unclear. This study aims to investigate the mechanisms of PDT in the treatment of CCA and try to improve the therapeutic effect of PDT by intervening associated signaling pathways.
METHODS
The Cell Counting Kit-8 (CCK-8) was used to examine the cytotoxicity of CCA cell lines following PDT. Apoptosis and reactive oxygen species (ROS) levels were measured by flow cytometry. A transmission electron microscope was used to study the changes in cell mitochondria after PDT. The levels of glutathione (GSH), malondialdehyde (MDA), ferrous iron (Fe), lactate dehydrogenase (LDH), and lipid peroxide (LPO) were determined. Changes in the expression of apoptosis and ferroptosis-related proteins were determined using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Xenograft tumor models were developed to investigate the effects of PDT on tumor proliferation, apoptosis, and ferroptosis in vivo.
RESULTS
PDT inhibited tumor proliferation and induced apoptosis both in vivo and in vitro. This treatment led to swelling and damage of the mitochondria in affected cells. Furthermore, ROS levels rose, accompanied by an increase in the proportion of apoptotic-positive cells. The expressions of Bax and Caspase-3 were upregulated, while the Bcl-2 was downregulated. Meanwhile, PDT triggered ferroptosis, marked by decreased expressions of GPX4 and SLC7A11, and reduced GSH levels. This was accompanied by upregulation of P53 expression and heightened levels of Fe, LPO, MDA, and LDH. After inducing the ferroptosis pathway, the therapeutic effect of PDT was enhanced, the tumor tissue was further reduced, and the degree of malignancy was reduced.
CONCLUSION
PDT promotes apoptosis and ferroptosis of cholangiocarcinoma cells by activating the P53/SLC7A11/GPX4 signaling pathway and inhibits the growth of cholangiocarcinoma. Inducing ferroptosis can enhance the effectiveness of photodynamic therapy.
Topics: Cholangiocarcinoma; Photochemotherapy; Ferroptosis; Phospholipid Hydroperoxide Glutathione Peroxidase; Apoptosis; Humans; Cell Line, Tumor; Animals; Signal Transduction; Tumor Suppressor Protein p53; Mice; Photosensitizing Agents; Bile Duct Neoplasms; Amino Acid Transport System y+; Reactive Oxygen Species; Cell Proliferation; Porphyrins; Xenograft Model Antitumor Assays
PubMed: 38679154
DOI: 10.1016/j.pdpdt.2024.104104 -
Photodiagnosis and Photodynamic Therapy Jun 2024Hematoporphyrin derivatives (HPD)-Photodynamic therapy (PDT) in combination with cisplatin (DDP) is an effective anticancer strategy. However, whether the order of...
BACKGROUND
Hematoporphyrin derivatives (HPD)-Photodynamic therapy (PDT) in combination with cisplatin (DDP) is an effective anticancer strategy. However, whether the order of combination affects efficacy has not been studied.
METHODS
The human lung adenocarcinoma (LUAD) A549 cells were used as the study subjects. After A549 cells were treated with a single medication (PDT/DDP) or a sequential combination (PDT + DDP / DDP + PDT), the cell viability was assayed using the cell counting kit-8 method. Hoechst staining, Annexin-V/propidium iodide (PI) double staining, western blotting, and a real-time quantitative polymerase chain reaction (RT-qPCR) were performed to examine the mechanisms behind the combined effects.
RESULTS
A synergistic impact between HPD-PDT and DDP was found. The cell viability in the PDT+DDP group was significantly lower than in the DDP+PDT group. A significant apoptotic profile and a high apoptotic rate were seen in the PDT + DDP group. The western blot showed that the expression levels of Bcl2-associated x(Bax) and cleaved-poly ADP-ribose polymerase (PARP) increased, and those of B-cell lymphoma-2 (Bcl-2) and Caspase-9 decreased in the PDT + DDP group. At the same time, the RT-qPCR revealed the upregulation of Bax and PARP mRNA and the downregulation of Bcl-2 and Caspase-9 mRNA.
CONCLUSION
The order of the combination therapy (PDT + DDP / DDP + PDT) was important. The HPD-PDT followed by DDP significantly inhibited LUAD cell viability, which may be related to the mitochondrial apoptotic pathway.
Topics: Humans; Photochemotherapy; Cisplatin; Photosensitizing Agents; Cell Survival; Apoptosis; Lung Neoplasms; Antineoplastic Agents; A549 Cells; Adenocarcinoma; Adenocarcinoma of Lung; Hematoporphyrins; Hematoporphyrin Derivative; Cell Line, Tumor
PubMed: 38679153
DOI: 10.1016/j.pdpdt.2024.104102 -
Journal of Photochemistry and... Jun 2024The objective of this study is to investigate the variances in transcriptome gene expression of normal oral mucosa-derived mesenchymal stem cell (OM-MSC), oral...
Differences in the response of normal oral mucosa, oral leukoplakia, oral squamous cell carcinoma-derived mesenchymal stem cells, and epithelial cells to photodynamic therapy.
OBJECTIVE
The objective of this study is to investigate the variances in transcriptome gene expression of normal oral mucosa-derived mesenchymal stem cell (OM-MSC), oral leukoplakia-derived MSC (OLK-MSC) and oral squamous cell carcinoma-derived MSC(OSCC-MSC). as Additionally, the study aims to compare the in vitro proliferation, migration, invasion ability, and response to photodynamic therapy (PDT) of these three MSC, HOK, DOK, leuk1, and Cal27 cell lines.
METHODS
HOK, DOK, leuk1, Cal27 cells were cultured in vitro. 3 MSC cells were obtained from OM, OLK, OSCC tissue (n = 3) and identified through flow cytometry. They were also cultured in vitro for osteogenic and lipogenic-induced differentiation. Based on the Illumina HiSeq high-throughput sequencing platform, OM-MSC, OLK-MSC, OSCC-MSC (n = 3) were subjected to transcriptome sequencing, functional annotation, and enrichment analysis of differentially expressed genes and related genes. CCK8 assay, wound healing assay, and transwell assay were performed to compare the proliferation, migration, and invasion of the seven types of cells. The 7 cells were incubated with 0, 0.125 mM, 0.25 mM, 0.5 mM, 1 mM, and 2 mM of the photosensitizer (5-aminolevulinic acid, 5-ALA) in vitro. Subsequently, they were irradiated with a 150 mM, 635 nm laser for 1 min, and the cell activity was detected using the CCK8 assay after 24 h. The mitochondrial changes in the 7 cells before and after the treatment of PDT were detected using the JC-10 probe, and the changes in ATP content were measured before and after the PDT treatment.
RESULTS
OM-MSC, OLK-MSC, and OSCC-MSC expressed positive MSC surface markers. After osteogenic and lipogenic-induced differentiation culture, stained calcium nodules and lipid droplets were visible, meeting the identification criteria of MSC. Pathway enrichment analysis revealed that the differentially expressed genes (DEGs) of OSCC-MSC compared to OLK-MSC were primarily associated with the PI3K-Akt signaling pathway and tumor-related pathways. OSCC-MSC exhibited stronger migratory and invasive abilities compared to Cal27. The IC50 values required for OM, OLK, and OSCC-derived MSC were lower than those required for epithelial cells treated with PDT, which were 1.396 mM, 0.9063 mM, and 2.924 mM, respectively. Cell membrane and mitochondrial disruption were observed in seven types of cells after 24 h of PDT treatment. However, HOK, DOK, leuk1, and Cal27 cells had an ATP content increased.
CONCLUSIONS
OLK, OSCC epithelial cells require higher concentrations of 5-ALA for PDT treatment than MSC of the same tissue origin. The concentration of 5-ALA required increases with increasing cell malignancy. Differences in the response of epithelial cells and MSC to PDT treatment may have varying impacts on OLK recurrence and malignancy.
Topics: Humans; Photochemotherapy; Mesenchymal Stem Cells; Mouth Mucosa; Leukoplakia, Oral; Cell Proliferation; Cell Movement; Carcinoma, Squamous Cell; Mouth Neoplasms; Epithelial Cells; Photosensitizing Agents; Cell Line, Tumor; Aminolevulinic Acid; Cell Differentiation; Transcriptome
PubMed: 38677259
DOI: 10.1016/j.jphotobiol.2024.112907 -
Molecules (Basel, Switzerland) Apr 2024The integration of a multidimensional treatment dominated by active ingredients of traditional Chinese medicine (TCM), including enhanced chemotherapy and...
The integration of a multidimensional treatment dominated by active ingredients of traditional Chinese medicine (TCM), including enhanced chemotherapy and synergistically amplification of oxidative damage, into a nanoplatform would be of great significance for furthering accurate and effective cancer treatment with the active ingredients of TCM. Herein, in this study, we designed and synthesized four matrine-proteolysis-targeting chimeras (PROTACs) (depending on different lengths of the chains named LST-1, LST-2, LST-3, and LST-4) based on PROTAC technology to overcome the limitations of matrine. LST-4, with better anti-tumor activity than matrine, still degrades p-Erk and p-Akt proteins. Moreover, LST-4 NPs formed via LST-4 self-assembly with stronger anti-tumor activity and glutathione (GSH) depletion ability could be enriched in lysosomes through their outstanding enhanced permeability and retention (EPR) effect. Then, we synthesized LST-4@ZnPc NPs with a low-pH-triggered drug release property that could release zinc(II) phthalocyanine (ZnPc) in tumor sites. LST-4@ZnPc NPs combine the application of chemotherapy and phototherapy, including both enhanced chemotherapy from LST-4 NPs and the synergistic amplification of oxidative damage, through increasing the reactive oxygen species (ROS) by photodynamic therapy (PDT), causing an GSH decrease via LST-4 mediation to effectively kill tumor cells. Therefore, multifunctional LST-4@ZnPc NPs are a promising method for killing cancer cells, which also provides a new paradigm for using natural products to kill tumors.
Topics: Matrines; Alkaloids; Reactive Oxygen Species; Quinolizines; Glutathione; Humans; Isoindoles; Animals; Indoles; Mice; Cell Line, Tumor; Zinc Compounds; Organometallic Compounds; Antineoplastic Agents; Neoplasms; Photochemotherapy; Proteolysis; Nanoparticles
PubMed: 38675664
DOI: 10.3390/molecules29081845 -
International Journal of Molecular... Apr 2024Thyroid cancer, particularly undifferentiated tumors, poses a significant challenge due to its limited response to standard therapies. The incidence of thyroid cancer,... (Review)
Review
Thyroid cancer, particularly undifferentiated tumors, poses a significant challenge due to its limited response to standard therapies. The incidence of thyroid cancer, predominantly differentiated carcinomas, is on the rise globally. Anaplastic thyroid carcinoma (ATC), though rare, is highly aggressive and challenging to treat. Therefore, this study aimed to collect data and explore alternative treatments, focusing on the efficacy of photodynamic therapy (PDT) combined with natural compounds as well as the potential role of phytochemicals, including quercetin, kaempferol, apigenin, genistein, daidzein, naringenin, hesperitin, anthocyanidins, epigallocatechin gallate (EGCG), resveratrol, ellagic acid, ferulic acid, caffeic acid, curcumin, saponins, ursolic acid, indole-3-carbinol (I3C), capsaicin, and piperine in thyroid cancer treatment. PDT, utilizing sensitizers activated by tumor-directed light, demonstrates promising specificity compared to traditional treatments. Combining PDT with natural photosensitizers, such as hypericin and genistein, enhances cytotoxicity against thyroid carcinoma cells. This literature review summarizes the current knowledge on phytochemicals and their anti-proliferative effects in in vitro and in vivo studies, emphasizing their effectiveness and mechanism of action as a novel therapeutic approach for thyroid cancers, especially those refractory to standard treatments.
Topics: Humans; Thyroid Neoplasms; Phytochemicals; Animals; Photochemotherapy; Phytotherapy; Clinical Trials as Topic; Plant Extracts
PubMed: 38674046
DOI: 10.3390/ijms25084463 -
International Journal of Molecular... Apr 2024Photodynamic therapy is expected to be a less invasive treatment, and strategies for targeting mitochondria, the main sources of singlet oxygen, are attracting attention...
Photodynamic therapy is expected to be a less invasive treatment, and strategies for targeting mitochondria, the main sources of singlet oxygen, are attracting attention to increase the efficacy of photodynamic therapy and reduce its side effects. To date, we have succeeded in encapsulating the photosensitizer rTPA into MITO-Porter (MP), a mitochondria-targeted Drug Delivery System (DDS), aimed at mitochondrial delivery of the photosensitizer while maintaining its activity. In this study, we report the results of our studies to alleviate rTPA aggregation in an effort to improve drug efficacy and assess the usefulness of modifying the rTPA side chain to improve the mitochondrial retention of MITO-Porter, which exhibits high therapeutic efficacy. Conventional rTPA with anionic side chains and two rTPA analogs with side chains that were converted to neutral or cationic side chains were encapsulated into MITO-Porter. Low-MP (MITO-Porter with Low Drug/Lipid) exhibited high drug efficacy for all three types of rTPA, and in Low-MP, charged rTPA-encapsulated MP exhibited high drug efficacy. The cellular uptake and mitochondrial translocation capacities were similar for all particles, suggesting that differences in aggregation rates during the incorporation of rTPA into MITO-Porter resulted in differences in drug efficacy.
Topics: Photosensitizing Agents; Mitochondria; Humans; Photochemotherapy; Porphyrins; Hydrophobic and Hydrophilic Interactions; Nanoparticles; Drug Delivery Systems; Cell Line, Tumor; Singlet Oxygen
PubMed: 38673875
DOI: 10.3390/ijms25084294 -
International Journal of Molecular... Apr 2024Fluorescence lifetime imaging (FLIM) and confocal fluorescence studies of a porphyrin-based photosensitiser (meso-tetraphenylporphine disulfonate: TPPS) were evaluated...
Fluorescence lifetime imaging (FLIM) and confocal fluorescence studies of a porphyrin-based photosensitiser (meso-tetraphenylporphine disulfonate: TPPS) were evaluated in 2D monolayer cultures and 3D compressed collagen constructs of a human ovarian cancer cell line (HEY). TPPS is known to be an effective model photosensitiser for both Photodynamic Therapy (PDT) and Photochemical Internalisation (PCI). This microspectrofluorimetric study aimed firstly to investigate the uptake and subcellular localisation of TPPS, and evaluate the photo-oxidative mechanism using reactive oxygen species (ROS) and lipid peroxidation probes combined with appropriate ROS scavengers. Light-induced intracellular redistribution of TPPS was observed, consistent with rupture of endolysosomes where the porphyrin localises. Using the same range of light doses, time-lapse confocal imaging permitted observation of PDT-induced generation of ROS in both 2D and 3D cancer models using fluorescence-based ROS together with specific ROS inhibitors. In addition, the use of red light excitation of the photosensitiser to minimise auto-oxidation of the probes was investigated. In the second part of the study, the photophysical properties of TPPS in cells were studied using a time-domain FLIM system with time-correlated single photon counting detection. Owing to the high sensitivity and spatial resolution of this system, we acquired FLIM images that enabled the fluorescence lifetime determination of the porphyrin within the endolysosomal vesicles. Changes in the lifetime dynamics upon prolonged illumination were revealed as the vesicles degraded within the cells.
Topics: Humans; Photosensitizing Agents; Porphyrins; Reactive Oxygen Species; Cell Line, Tumor; Photochemotherapy; Optical Imaging; Lysosomes; Female; Ovarian Neoplasms
PubMed: 38673807
DOI: 10.3390/ijms25084222 -
International Journal of Molecular... Apr 2024Bone tumors, particularly osteosarcoma, are prevalent among children and adolescents. This ailment has emerged as the second most frequent cause of cancer-related... (Review)
Review
Bone tumors, particularly osteosarcoma, are prevalent among children and adolescents. This ailment has emerged as the second most frequent cause of cancer-related mortality in adolescents. Conventional treatment methods comprise extensive surgical resection, radiotherapy, and chemotherapy. Consequently, the management of bone tumors and bone regeneration poses significant clinical challenges. Photothermal tumor therapy has attracted considerable attention owing to its minimal invasiveness and high selectivity. However, key challenges have limited its widespread clinical use. Enhancing the tumor specificity of photosensitizers through targeting or localized activation holds potential for better outcomes with fewer adverse effects. Combinations with chemotherapies or immunotherapies also present avenues for improvement. In this review, we provide an overview of the most recent strategies aimed at overcoming the limitations of photothermal therapy (PTT), along with current research directions in the context of bone tumors, including (1) target strategies, (2) photothermal therapy combined with multiple therapies (immunotherapies, chemotherapies, and chemodynamic therapies, magnetic, and photodynamic therapies), and (3) bifunctional scaffolds for photothermal therapy and bone regeneration. We delve into the pros and cons of these combination methods and explore current research focal points. Lastly, we address the challenges and prospects of photothermal combination therapy.
Topics: Humans; Bone Neoplasms; Photothermal Therapy; Infrared Rays; Animals; Photosensitizing Agents; Osteosarcoma; Combined Modality Therapy; Immunotherapy; Photochemotherapy; Bone Regeneration
PubMed: 38673726
DOI: 10.3390/ijms25084139 -
Biomolecules Apr 2024In cancer therapy, photodynamic therapy (PDT) has attracted significant attention due to its high potential for tumor-selective treatment. However, PDT agents often...
In cancer therapy, photodynamic therapy (PDT) has attracted significant attention due to its high potential for tumor-selective treatment. However, PDT agents often exhibit poor physicochemical properties, including solubility, necessitating the development of nanoformulations. In this study, we developed two cationic peptide-based self-assembled nanomaterials by using a PDT agent, chlorin e6 (Ce6). To manufacture biocompatible nanoparticles based on peptides, we used the cationic poly-L-lysine peptide, which is rich in primary amines. We prepared low- and high-molecular-weight poly-L-lysine, and then evaluated the formation and performance of nanoparticles after chemical conjugation with Ce6. The results showed that both molecules formed self-assembled nanoparticles by themselves in saline. Interestingly, the high-molecular-weight poly-L-lysine and Ce6 conjugates (HPLCe6) exhibited better self-assembly and PDT performance than low-molecular-weight poly-L-lysine and Ce6 conjugates (LPLCe6). Moreover, the HPLCe6 conjugates showed superior cellular uptake and exhibited stronger cytotoxicity in cell toxicity experiments. Therefore, it is functionally beneficial to use high-molecular-weight poly-L-lysine in the manufacturing of poly-L-lysine-based self-assembling biocompatible PDT nanoconjugates.
Topics: Polylysine; Chlorophyllides; Porphyrins; Humans; Photochemotherapy; Nanoparticles; Photosensitizing Agents; Molecular Weight; Cell Survival
PubMed: 38672448
DOI: 10.3390/biom14040431