pheophorbide-a has been researched along with Neoplasms* in 15 studies
1 review(s) available for pheophorbide-a and Neoplasms
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The chlorophyll catabolite pheophorbide a as a photosensitizer for the photodynamic therapy.
Pheophorbide a is a clorophyll catabolite that recently has drawn the attention of several investigators for its potential in photodynamic therapy. In this review we summarize its photophysical properties, phototoxicity, cellular localization, biodistribution and PDT activity as a free or conjugated molecule. Topics: Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carrier Proteins; Cell Survival; Chlorophyll; Humans; Neoplasms; Photochemotherapy; Photosensitizing Agents | 2012 |
14 other study(ies) available for pheophorbide-a and Neoplasms
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A Phenylfurocoumarin Derivative Reverses ABCG2-Mediated Multidrug Resistance In Vitro and In Vivo.
Topics: Animals; Antineoplastic Agents; ATP Binding Cassette Transporter, Subfamily G, Member 2; Biological Transport; Cell Proliferation; Chlorophyll; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Flow Cytometry; Furocoumarins; HCT116 Cells; Heterografts; High-Throughput Screening Assays; Humans; Irinotecan; Mice; Neoplasm Proteins; Neoplasms | 2021 |
Optimized Combination of Photodynamic Therapy and Chemotherapy Using Gelatin Nanoparticles Containing Tirapazamine and Pheophorbide a.
In combination therapy, synergetic effects of drugs and their efficient delivery are essential. Herein, we screened 12 anticancer drugs for combination with photodynamic therapy (PDT) using pheophorbide a (Pba). On the basis of combination index (CI) values in cell viability tests, we selected tirapazamine (TPZ) and developed self-assembled gelatin nanoparticles (NPs) containing both Pba and TPZ. The resulting TPZ-Pba-NPs showed a synergetic effect to kill tumor cells because TPZ was activated under the hypoxic conditions that originated from the PDT with Pba and laser irradiation. After they were injected into tumor-bearing mice via the tail vein, TPZ-Pba-NPs showed 3.17-fold higher blood concentration and 4.12-fold higher accumulation in tumor tissue 3 and 24 h postinjection, respectively. Upon laser irradiation to tumor tissue, TPZ-Pba-NPs successfully suppressed tumor growth by efficient drug delivery and synergetic effects Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Chlorophyll; Drug Carriers; Drug Screening Assays, Antitumor; Drug Synergism; Drug Therapy; Gelatin; Light; Mice, Inbred C3H; Nanoparticles; Neoplasms; Photochemotherapy; Photosensitizing Agents; Reactive Oxygen Species; Tirapazamine | 2021 |
Chitosan capped pH-responsive hollow mesoporous silica nanoparticles for targeted chemo-photo combination therapy.
Combination therapy provides an efficient way to overcome the potential multidrug resistance and enhance anticancer efficacy. In this work, a biodegradable pH-responsive hollow mesoporous silica nanoparticle (HMSN-GM-CS-FA) was developed for co-delivery of pheophorbide a (PA) and doxorubicin (DOX). This drug delivery system possessed controlled particle size and larger inner hollow core, which endowed the nanoparticle with excellent encapsulation capacities. The uptake efficiency of drug loaded nanoparticles HMSNs-GM-CS-FA@DOX/PA in cancer cells was greatly improved by folic acid-mediated endocytosis. The nanocarrier showed excellent drug controlled release properties based on the pH-dependent swelling effect of the coating layer. More importantly, the nanoplatform could fully combine photothermal-, photodynamic- and chemotherapies to develop synergistic antitumor efficacy. This strategy of integrating multi-therapeutic functions in one single formulation promised a powerful route to construct intelligent co-delivery carriers for efficient combinational clinical application. Topics: Antineoplastic Agents; Chitosan; Chlorophyll; Combined Modality Therapy; Doxorubicin; Drug Delivery Systems; Drug Liberation; Drug Resistance, Multiple; Endocytosis; Humans; Hydrogen-Ion Concentration; Metal Nanoparticles; Neoplasms; Silicon Dioxide | 2020 |
Self-Amplified Drug Delivery with Light-Inducible Nanocargoes to Enhance Cancer Immunotherapy.
Chemoimmunotherapy by systemic administration of individual regimens suffers from inconsistent pharmacokinetics profiles, low tumor specificity, and severe side effects. Despite promising nanoparticle-based codelivery approaches in therapeutics, the pathophysiological barriers of solid tumors are a hurdle for tumor accumulation and deep penetration of the drug-loaded nanoparticles. A light-inducible nanocargo (LINC) for immunotherapy is reported. LINC is composed of a reduction-responsive heterodimer of photosensitizer pheophorbide A (PPa) and indoleamine 2,3-dioxygenase 1 (IDO-1) inhibitor, i.e., NLG919, and a light-activatable prodrug of oxaliplatin (OXA). LINC administrated through intravenous injection is passively accumulated at the tumor site to generate near-infrared (NIR) fluorescence signal. Under fluorescence imaging guidance, the first-wave of NIR laser irradiation induce reactive oxygen species (ROS) generation, trigger cleavage of the polyethylene glycol (PEG) corona, and thus promote tumor retention and deep penetration of LINC. When exposed to the second-wave NIR laser illumination, LINC efficiently elicits the immune response and promotes intratumoral infiltration of cytotoxic T lymphocytes (CTLs). Furthermore, NLG919 delivered by LINC reverses the immunosuppressive tumor microenvironment by suppressing IDO-1 activity. Chemoimmunotherapy with LINC inhibit the tumor growth, lung metastasis, and tumor recurrence. The light-inducible self-amplification strategy for improved drug delivery and immunotherapy shows potential. Topics: Animals; Chlorophyll; Dimerization; Drug Carriers; Immunotherapy; Light; Mice; Mice, Inbred BALB C; Nanostructures; Neoplasms; Photochemotherapy; Photosensitizing Agents; Reactive Oxygen Species; T-Lymphocytes, Cytotoxic | 2019 |
NIR-responsive ROS generating core and ROS-triggered 5'-Deoxy-5-fluorocytidine releasing shell structured water-swelling microgel for locoregional combination cancer therapy.
Combination chemotherapy now becomes the most standard cancer treatment protocol. Here, we present a core-shell type polymeric microgel (CSPM) which combines photodynamic and chemo therapeutic modalities in one-pot system. CSPM localizes in the malignant lesion after intratumoral injection, releases reactive oxygen species (ROS) and anticancer drug (5'-deoxy-5-fluorocytidine; DFCR) under the near-infrared (NIR) laser treatment. Pheophorbide A (PheoA)-linked poly(hydroxyethyl methacrylate) (poly-HEMA) was designated to a ROS-generating core, and chemically covered with a chitosan shell. In addition, phenylboronic acid was employed in chitosan shells and linked to DFCR to form an ROS cleavable boronic ester. The core-shell structure of CSPM was determined by transmission electron microscopy. NIR-responsive photodynamic ROS generation was confirmed by the oxidative reduction of 9,10-dimethylanthracene (a fluorescent dye), and the cascadic release of DFCR by ROS was confirmed by a release study and a live and dead cell imaging study. Typically, poly-HEMA cored microgel increased its volume by 48.9-fold after absorption of body fluid. This swelling property ensured CSPM was retained in tumor tissues after subtumoral injection and the suitability of CSPM for locoregional phototherapy. The therapeutic effect of CSPM was attributed to the combined, cascadic deliveries of cytotoxic ROS and DFCR and confirmed by growth inhibition studies in in vitro pancreatic cancer cells and in vivo colon cancer mouse model. Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Chlorophyll; Combined Modality Therapy; Delayed-Action Preparations; Deoxycytidine; Humans; Infrared Rays; Laser Therapy; Mice, Inbred BALB C; Microgels; Neoplasms; Polyhydroxyethyl Methacrylate; Reactive Oxygen Species; Water | 2019 |
Vitamin Bc -Bearing Hydrophilic Photosensitizer Conjugate for Photodynamic Cancer Theranostics.
The accurate diagnosis and proper therapy for cancer are essential to improve the success rate of cancer treatment. Here, we demonstrated that the vitamin Bc -bearing hydrophilic photosensitizer conjugate folic acid-polyethylene glycol-pheophorbideA (FA-PEG-PheoA) has been synthesized for the intracellular diagnosis and photodynamic therapy of a tumor. The synthesized vitamin Bc -bearing hydrophilic photosensitizer conjugate has been characterized for the folic acid receptor expressing the ability to target tumor cells, which is facilitated by the chemical conjugation with folic acid. The vitamin Bc -bearing hydrophilic photosensitizer conjugate internalization mechanism was identified through a competitive inhibition test with free folic acid. We optimized the laser-sensitive, cytotoxicity changeable, vitamin Bc -bearing hydrophilic photosensitizer conjugate concentration, which is non-cytotoxic under normal conditions and specifically cytotoxic toward cancer cells (maximum 69.15%) under laser irradiation conditions used for theranostic agents. The cancer therapeutic and diagnosis effects of synthesized conjugate were confirmed in MDA-MB-231 cells and MDA-MB-231-bearing mice. As a result, the vitamin Bc -bearing hydrophilic photosensitizer conjugate exhibited a highly photodynamic therapeutic effect, which enabled the selective detection of a folic acid receptor expressing cancer using optical imaging. Topics: Animals; Cell Line, Tumor; Chlorophyll; Folic Acid; Humans; Hydrophobic and Hydrophilic Interactions; Mice; Nanoparticles; Neoplasms; Photochemotherapy; Photosensitizing Agents; Polyethylene Glycols; Theranostic Nanomedicine; Thiamine; Xenograft Model Antitumor Assays | 2015 |
Smart Probe for Tracing Cancer Therapy: Selective Cancer Cell Detection, Image-Guided Ablation, and Prediction of Therapeutic Response In Situ.
Integrated diagnosis and therapy systems that can offer traceable cancer therapy are in high demand for personalized medicine. Herein, a pH-responsive polymeric probe containing tetraphenylsilole (TPS) with aggregation-induced emission characteristics and pheophorbide A (PheA) photosensitizer (PS) with aggregation-caused quenching property for tracing the whole process of cancer therapy is reported. At physiological conditions (pH 7.4), the probe self-assembles into nanoparticles (NPs), which show weak fluorescence of PheA with low phototoxicity, but strong green fluorescence from TPS for probe self-tracking. Upon uptake by cancer cells and entrapment in lysosomes (pH 5.0), the NPs disassemble to yield weak emission of TPS but strong red fluorescence of PheA with restored phototoxicity for PS activation monitoring. Upon light irradiation, the generated reactive oxygen species can cause lysosomal disruption to trigger cell apoptosis. Meanwhile, the probe leaks to the cytoplasm (pH 7.2), where the TPS fluorescence is restored for in situ visualization of the therapeutic response. The probe design thus represents a novel strategy for traceable cancer therapy. Topics: Apoptosis; Cell Line, Tumor; Chlorophyll; Cytoplasm; Cytosol; Fluorescent Dyes; Green Fluorescent Proteins; HEK293 Cells; Humans; Hydrogen-Ion Concentration; Lysosomes; MCF-7 Cells; Microscopy, Fluorescence; Nanoparticles; Neoplasms; Photosensitizing Agents; Polylysine; Polymers; Precision Medicine; Reactive Oxygen Species | 2015 |
The sensitivity of cancer cells to pheophorbide a-based photodynamic therapy is enhanced by Nrf2 silencing.
Photodynamic therapy (PDT) has emerged as an effective treatment for various solid tumors. The transcription factor NRF2 is known to protect against oxidative and electrophilic stress; however, its constitutive activity in cancer confers resistance to anti-cancer drugs. In the present study, we investigated NRF2 signaling as a potential molecular determinant of pheophorbide a (Pba)-based PDT by using NRF2-knockdown breast carcinoma MDA-MB-231 cells. Cells with stable NRF2 knockdown showed enhanced cytotoxicity and apoptotic/necrotic cell death following PDT along with increased levels of singlet oxygen and reactive oxygen species (ROS). A confocal microscopic visualization of fluorogenic Pba demonstrated that NRF2-knockdown cells accumulate more Pba than control cells. A subsequent analysis of the expression of membrane drug transporters showed that the basal expression of BCRP is NRF2-dependent. Among measured drug transporters, the basal expression of breast cancer resistance protein (BCRP; ABCG2) was only diminished by NRF2-knockdown. Furthermore, after incubation with the BCRP specific inhibitor, differential cellular Pba accumulation and ROS in two cell lines were abolished. In addition, NRF2-knockdown cells express low level of peroxiredoxin 3 compared to the control, which implies that diminished mitochondrial ROS defense system can be contributing to PDT sensitization. The role of the NRF2-BCRP pathway in Pba-PDT response was further confirmed in colon carcinoma HT29 cells. Specifically, NRF2 knockdown resulted in enhanced cell death and increased singlet oxygen and ROS levels following PDT through the diminished expression of BCRP. Similarly, PDT-induced ROS generation was substantially increased by treatment with NRF2 shRNA in breast carcinoma MCF-7 cells, colon carcinoma HCT116 cells, renal carcinoma A498 cells, and glioblastoma A172 cells. Taken together, these results indicate that the manipulation of NRF2 can enhance Pba-PDT sensitivity in multiple cancer cells. Topics: ATP Binding Cassette Transporter, Subfamily G, Member 2; ATP-Binding Cassette Transporters; Breast Neoplasms; Cell Line, Tumor; Chlorophyll; Colonic Neoplasms; Female; Gene Knockdown Techniques; Gene Silencing; Genetic Vectors; Humans; Laser Therapy; Lasers; Lentivirus; Neoplasm Proteins; Neoplasms; NF-E2-Related Factor 2; Peroxiredoxin III; Photochemotherapy; Radiation-Sensitizing Agents; Reactive Oxygen Species; RNA, Small Interfering; Transduction, Genetic | 2014 |
Cancer cell-specific photoactivity of pheophorbide a-glycol chitosan nanoparticles for photodynamic therapy in tumor-bearing mice.
We designed a cancer-cell specific photosensitizer nano-carrier by synthesizing pheophorbide a (PheoA) conjugated glycol chitosan (GC) with reducible disulfide bonds (PheoA-ss-GC). The amphiphilic PheoA-ss-GC conjugates self-assembled in aqueous condition to form core-shell structured nanoparticles (PheoA-ss-CNPs) with good colloidal stability and switchable photoactivity. The photoactivity of PheoA-ss-CNPs in an aqueous environment was greatly suppressed by the self-quenching effect, which enabled the PheoA-ss-CNPs to remain photo-inactive and in a quenched state. However, after the cancer cell-specific uptake, the nanoparticular structure instantaneously dissociated by reductive cleavage of the disulfide linkers, followed by an efficient dequenching process. Compared to non-reducible PheoA-conjugated GC-NPs with stable amide linkages (PheoA-CNPs), PheoA-ss-CNPs rapidly restored their photoactivity in response to intracellular reductive conditions, thus presenting higher cytotoxicity with light treatment. In addition, the PheoA-ss-CNPs presented prolonged blood circulation in vivo compared to free PheoA, demonstrating enhanced tumor specific targeting behavior through the enhanced permeation and retention (EPR) effect. The enhanced tumor accumulation of PheoA-ss-CNPs enabled tumor therapeutic efficacy that was more efficient than free PheoA in tumor-bearing mice. Based on the enhanced intracellular release for cytosolic high dose and switchable photoactivity mechanism for reduced side effects, these results suggest that PheoA-ss-CNPs have good potential for photodynamic therapy (PDT) in cancer treatment. Topics: Animals; Chitosan; Chlorophyll; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Nanoparticles; Neoplasms; Oxidation-Reduction; Photochemotherapy; Radiation-Sensitizing Agents | 2013 |
GSH-mediated photoactivity of pheophorbide a-conjugated heparin/gold nanoparticle for photodynamic therapy.
In this study, we developed a new photosensitizer (PS)-conjugated hybrid nanoparticle comprised of gold nanoparticle (AuNP) as an efficient energy quencher, polysaccharide heparin and a second generation PS, pheophorbide a (PhA) for PDT. The hybrid nanoparticles (PhA-H/AuNPs) with an average size of 40nm were prepared by surface coating of AuNPs with PhA conjugated heparins via gold-thiol interaction. The glutathione (GSH)-mediated switchable photoactivity of the PhA-H/AuNPs was observed by fluorescence quenching and dequenching behaviors in the absence and presence of GSH. The photoactivity was significantly suppressed in aqueous media, but instantaneously restored at the GSH-rich intracellular environment to generate a strong fluorescence signal together with active production of singlet oxygen species with light treatment. In vitro cell tests revealed marked phototoxicity and high intracellular uptake of PhA-H/AuNPs in contrast with free PhA. The PhA-H/AuNPs also exhibited a prolonged circulation characteristic, enhanced tumor specificity, and improved photodynamic therapeutic efficacy compared with free PhA in tumor-bearing mice. As a result, the PhA-H/AuNPs may serve as an effective smart nanomedicine platform for PDT and have great potential for the clinical treatment of various tumors. Topics: Animals; Cell Line, Tumor; Chlorophyll; Drug Carriers; Glutathione; Gold; Heparin; Humans; Light; Metal Nanoparticles; Mice; Mice, Nude; Neoplasms; Photochemotherapy; Photosensitizing Agents; Tumor Burden | 2013 |
Use of baculovirus BacMam vectors for expression of ABC drug transporters in mammalian cells.
ATP-binding cassette (ABC) drug transporters ABCB1 [P-glycoprotein (Pgp)] and ABCG2 are expressed in many tissues including those of the intestines, the liver, the kidney and the brain and are known to influence the pharmacokinetics and toxicity of therapeutic drugs. In vitro studies involving their functional characteristics provide important information that allows improvements in drug delivery or drug design. In this study, we report use of the BacMam (baculovirus-based expression in mammalian cells) expression system to express and characterize the function of Pgp and ABCG2 in mammalian cell lines. BacMam-Pgp and BacMam-ABCG2 baculovirus-transduced cell lines showed similar cell surface expression (as detected by monoclonal antibodies with an external epitope) and transport function of these transporters compared to drug-resistant cell lines that overexpress the two transporters. Transient expression of Pgp was maintained in HeLa cells for up to 72 h after transduction (48 h after removal of the BacMam virus). These BacMam-baculovirus-transduced mammalian cells expressing Pgp or ABCG2 were used for assessing the functional activity of these transporters. Crude membranes isolated from these cells were further used to study the activity of these transporters by biochemical techniques such as photo-cross-linking with transport substrate and adenosine triphosphatase assays. In addition, we show that the BacMam expression system can be exploited to coexpress both Pgp and ABCG2 in mammalian cells to determine their contribution to the transport of a common anticancer drug substrate. Collectively, these data demonstrate that the BacMam-baculovirus-based expression system can be used to simultaneously study the transport function and biochemical properties of ABC transporters. Topics: Animals; Antineoplastic Agents; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily B, Member 1; ATP Binding Cassette Transporter, Subfamily G, Member 2; ATP-Binding Cassette Transporters; Baculoviridae; Biological Transport; Cell Line, Tumor; Cell Membrane; Chlorophyll; Doxorubicin; Drug Evaluation, Preclinical; Drug Resistance, Neoplasm; Genetic Vectors; Humans; Mammals; Mitoxantrone; Neoplasm Proteins; Neoplasms; Radiation-Sensitizing Agents; Recombinant Proteins; Transduction, Genetic | 2012 |
Synthesis of pheophorbide-a conjugates with anticancer drugs as potential cancer diagnostic and therapeutic agents.
Pheophorbide-a, a chlorine based photosensitizer known to be selectively accumulated in cancer cells, was conjugated with anticancer drugs, doxorubicin and paclitaxel in the purpose of selective cancer diagnosis and therapy. Pheophorbide-a was conjugated with anticancer drugs via directly and by the use of selective cleavage linkers in cancer cell. The fluorescence of pheophorbide-a and doxorubicin conjugate by excitation at 420 or 440 nm was greatly diminished possibly by the energy transfer mechanism between two fluorescent groups. However, upon treatment in cancer cells, the conjugate showed to be cleaved to restore each fluorescence of pheophorbide-a and doxorubicin after 48 h of incubation. Also, pheophorbide-a conjugates either with doxorubicin and paclitaxel inhibited the growth of various cancer cells more potently than pheophorbide-a, which displayed very weak inhibitory activity. The results indicated that the pheophorbide-a conjugates with anticancer drugs could be utilized for selective cancer therapy as well as for the fluorescence detection of cancer. Topics: Animals; Antineoplastic Agents; Cell Proliferation; Cell Survival; Chlorophyll; Dose-Response Relationship, Drug; Doxorubicin; Drug Screening Assays, Antitumor; Fluorescence; Fluorescent Dyes; HeLa Cells; Humans; Mice; Mice, Inbred C3H; Microscopy, Confocal; Molecular Conformation; Neoplasms; Paclitaxel; Spectrometry, Fluorescence; Stereoisomerism; Structure-Activity Relationship; Tissue Distribution; Tumor Cells, Cultured | 2011 |
Nrf2-dependent induction of human ABC transporter ABCG2 and heme oxygenase-1 in HepG2 cells by photoactivation of porphyrins: biochemical implications for cancer cell response to photodynamic therapy.
Photodynamic therapy is a recently developed anticancer treatment that utilizes the generation of singlet oxygen and other reactive oxygen species in cancer tissue. Nrf2, an NF-E2-related transcription factor, plays a pivotal role in transcriptional upregulation of many target genes, including those for metabolizing enzymes and transporters essential for cellular defense in response to oxidative stress. In the present study, we examined the potential involvement of Nrf2 in the induction of human ABC transporter ABCG2 and heme oxygenase-1 (HO-1). When HepG2 cells were incubated with non-toxic concentrations of delta-aminolevulinic acid, protoporphyrin IX, or pheophorbide a and then exposed to visible light for 90 min, the mRNA level of HO-1 began increasing markedly, reaching the maximal level in 4 h. Following the transient induction of HO-1, the mRNA level of ABCG2 gradually increased in a time-dependent manner, whereas the ABCB6 mRNA level was little affected. Nrf2-specific siRNA treatments suppressed the induction of both ABCG2 and HO-1 after the photoactivation of porphyrins, suggesting that Nrf2 is a common regulator for transcriptional activation of the ABCG2 and HO-1 genes. On the other hand, the mRNA level of HO-1 was remarkably enhanced by Zn(2+)-protoporphyrin IX or hemin even in the absence of light. This induction may be attributed to inactivation of Bach1, a repressor for the HO-1 gene, by those compounds. Since patients have demonstrated individual defferences in their response to photodynamic therapy, transcriptional activation of the ABCG2 and HO-1 genes in cancer cells may affect patients' responses to photodynamic therapy. Topics: Aminolevulinic Acid; ATP Binding Cassette Transporter, Subfamily G, Member 2; ATP-Binding Cassette Transporters; Benzothiazoles; Blotting, Western; Cell Line, Tumor; Chlorophyll; Chromatography, High Pressure Liquid; Diamines; Electrophoresis, Polyacrylamide Gel; Fluorescent Dyes; Heme Oxygenase-1; Humans; Neoplasm Proteins; Neoplasms; NF-E2-Related Factor 2; Organic Chemicals; Oxidative Stress; Photochemistry; Photochemotherapy; Photosensitizing Agents; Porphyrins; Protoporphyrins; Quinolines; RNA, Messenger; RNA, Small Interfering; Transfection | 2008 |
[Generation of active oxygen by environmental factors; pheophorbide].
Topics: Animals; Chlorophyll; Cholesterol; Free Radicals; Humans; Light; Neoplasms; Oxygen; Photochemistry; Photosensitivity Disorders | 1988 |