Design, synthesis and biological evaluation of folate-porphyrin: a new photosensitizer for targeted photodynamic therapy

2010 ◽  
Vol 14 (06) ◽  
pp. 547-555 ◽  
Author(s):  
Donghong Li ◽  
Junlin Diao ◽  
Dong Wang ◽  
Jianchang Liu ◽  
Jiaotao Zhang
Keyword(s):  
Photodynamic Therapy ◽  
Cellular Uptake ◽  
Hela Cells ◽  
Laser Scanning ◽  
Folate Receptor ◽  
Confocal Laser Scanning Microscope ◽  
Biological Evaluation ◽  
Confocal Laser ◽  
Targeted Photodynamic Therapy

A novel folate-porphyrin conjugate 1 for targeted photodynamic therapy of tumor was designed and synthesized. The results of fluorescence spectroscopy and confocal laser scanning microscope demonstrated that the cellular uptake of conjugate 1 by HeLa cells was 35 times higher than that of precursor porphyrin 3 after 24 h incubation, and that the presence of excessive free folic acid inhibited the cellular uptake of conjugate 1. Cytotoxicity against folate-receptor positive HeLa cells in vitro measured by MTT assay demonstrated that conjugate 1 exhibited much lower dark cytotoxicity but significant photocytotoxicity, with 86.4% of cell growth inhibition ratio after irradiation. However, conjugate 1 induced lower photocytotoxicity for normal cells and folate-receptor negative cells. These results suggest that folate-porphyrin like photosensitizers could induce a potentially useful targeted photodynamic therapy modality for folate-receptor-positive cancer cells due to the folate-receptor mediated endocytosis.

Synthesis, singlet oxygen generation, photocytotoxicity and subcellular localization of azobisporphyrins as potentially photodynamic therapeutic agents in vitro cell study

2017 ◽  
Vol 21 (02) ◽  
pp. 122-127 ◽  
Author(s):  
Yunman Zheng ◽  
Sizhe Zhu ◽  
Lijun Jiang ◽  
Fengshou Wu ◽  
Chi Huang ◽  
...  
Keyword(s):  
Singlet Oxygen ◽  
Hela Cells ◽  
Cellular Localization ◽  
Laser Scanning ◽  
Laser Scanning Confocal Microscopy ◽  
Confocal Laser Scanning Microscope ◽  
Confocal Laser ◽  
Oxygen Generation ◽  
Scanning Confocal Microscopy

Three azobisporphyrins (Por1, Por2 and Por3) were synthesized by coupling two molecules of (4-nitrophenyl/pyridyl) porphyrins in the presence of KOH/butanol. The structures of porphyrins were confirmed by UV, IR, NMR and mass spectra and elemental analysis. With tetraphenylporphyrin (H2TPP) as a control, the singlet oxygen (1O[Formula: see text] generation of porphyrins was evaluated through 1,3-diphenylisobenzofuran (DPBF) method. The order of ability to generate 1O2 for three azobisporphyrins was Por 1 [Formula: see text]Por 2 > Por 3[Formula: see text] H2TPP. The photocytotoxicity and sub-cellular localization of azobisporphyrins over Hela cells were studied through MTT analysis and confocal laser scanning microscope, respectively. The results indicated Por 1 and Por 2 displayed the low dark-cytotoxicity, while Por 3 induced a concentration-dependent cytotoxicity to Hela cells with the concentration of porphyrins ranging from 1 to 100 [Formula: see text] M. With the light dose at 4 J/cm2, Por 3 killed more than 60% Hela cells at 2 [Formula: see text] M, indicating a high photocytoxicity. As seen from the laser scanning confocal microscopy images, Por 3 was mainly localized in cell membrane, while Por 1 and Por 2 do not displayed significant fluorescent emission in Hela cells. These results suggest the synthesized cationic azobisporphyrin could be used as a potential therapeutic agent for photodynamic therapy of cancers.

A Facile Synthesis of Acid-Activatable Nanoparticles for Efficient Intracellular Doxorubicin Release

2017 ◽  
Vol 46 ◽  
pp. 20-30 ◽  
Author(s):  
Cao Ming ◽  
Xiao Wan Song ◽  
Yu Jiao Zhang ◽  
Chang Zhi Xu ◽  
Peng Chen ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Hela Cells ◽  
Laser Scanning ◽  
Human Cancer ◽  
Polymeric Nanoparticles ◽  
Confocal Laser Scanning Microscope ◽  
Ph Sensitive ◽  
Confocal Laser ◽  
Cell Nuclei

pH responsive polymeric nanoparticles have emerged as a promising technology platform for targeted and controlled drug delivery in recent years. In this paper, endosomal pH-activatable doxorubicin (DOX) and core-crosslinked polymeric nanoparticles (DCNPs) were prepared and investigated for potent growth inhibition of human cancer cells in vitro. In vitro drug release studies, DOX conjugated nanoparticles with hydrazone bond showed a pH sensitive release phenomenon, that is, the releasing is significantly faster at mildly acidic condition with pH of 5.5 than that at physiological condition. Confocal laser scanning microscope (CLSM) observations revealed that DOX conjugated nanoparticles delivered and released DOX into the cytosols as well as cell nuclei of Hela cells following 6 h incubation. MTT assays demonstrated that these pH-sensitive DOX nanoparticles exhibited high antitumor effect to HeLa cells. The conjugated DOX polymeric nanoparticles may be a promising candidate as a nanoscale and pH-sensitive drug delivery vehicle for cancer therapy.

scholarly journals Hyaluronic Acid-Decorated Laponite® Nanocomposites for Targeted Anticancer Drug Delivery

Polymers ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 137 ◽  
Author(s):  
Tingting Jiang ◽  
Guangxiang Chen ◽  
Xiangyang Shi ◽  
Rui Guo
Keyword(s):  
Hyaluronic Acid ◽  
Hela Cells ◽  
Laser Scanning ◽  
Drug Loading ◽  
Confocal Laser Scanning Microscope ◽  
Cancer Drug ◽  
Confocal Laser ◽  
Cell Viability Assay ◽  
Anticancer Drug Delivery

In this study, hyaluronic acid (HA), a natural polysaccharide that can specifically bind to CD44 receptors, was conjugated onto laponite® (LAP) nanodisks for the encapsulation and specific delivery of the anti-cancer drug doxorubicin (DOX) to CD44-overexpressed cancer cells. The prepared LM-HA could encapsulate DOX efficiently and release drug in a continuous manner with pH-responsiveness. In vitro cell viability assay proved that LM-HA had good biocompatibility, and drug-loaded LM-HA/DOX exhibited targeted anti-tumor effects against HeLa cells with CD44 receptors overexpressed. In addition, the flow cytometric detection and confocal laser scanning microscope results confirmed that LM-HA/DOX could be specifically internalized by HeLa cells via CD44-mediated endocytosis. Therefore, the HA-modified LAP nanodisks with high drug loading efficiency, pH-sensitive drug release properties and CD44 targetability might be an efficient nanoplatform for cancer chemotherapy.

scholarly journals Grape Seed Extract as a Potential Remineralizing Agent: A Comparative in vitro Study

2012 ◽  
Vol 13 (4) ◽  
pp. 425-430 ◽  
Author(s):  
Shiny Benjamin ◽  
Roshni LNU ◽  
Sabeena Susan Thomas ◽  
Mohan Thomas Nainan
Keyword(s):  
Laser Scanning ◽  
Grape Seed Extract ◽  
Grape Seed ◽  
Confocal Laser Scanning Microscope ◽  
Seed Extract ◽  
Confocal Laser ◽  
Scanning Microscope ◽  
Caries Lesions ◽  
Calcium Glycerophosphate

ABSTRACT Objective Remineralization is an effective treatment that may stop or reverse early tooth decay. Grape seed extract (GSE) is the potential remineralizing agent under investigation. Materials and methods Sound human tooth sections were obtained from the cervical portion of the root and stored in demineralizing solution at 37°C for 96 hours to induce artificial root caries lesions. The sections were divided into four treatment groups including 6.5% grape seed extract, sodium monofluorophosphate (220 ppm) with 0.05% calcium glycerophosphate, 0.5% calcium glycerophosphate and control (no treatment). An in vitro pH cycling model was used to cycle the demineralized specimens through treatment solutions, acidic buffer and neutral buffer for 8 days at 6 cycles per day. Subsequently, they were evaluated using confocal laser scanning microscope. Data were analyzed using analysis of variance (p < 0.05). Results GSE revealed less demineralization and more remineralization compared with other groups. Conclusion GSE promotes remineralization of artificial root caries lesions. Clinical significance The search for the perfect remineralizing agent continues to this day. GSE could be a welcome addition to the remineralization armamentarium. Abbreviations and acronyms GSE: Grape seed extract; ppm: Parts per million; CaGP: Calcium glycerophosphate; CLSM: Confocal laser scanning microscope; ANOVA: Analysis of variance; PA: Proanthocyanidin; CEJ: Cementoenamel junction; mM: Millimole; CaCl2.2H2O: Calcium chloride dihydrate; KH2PO4: Potassium dehydrate phosphate; K2HPO4: Dipotassium phosphate; dH2O: Deionized water; w/v: Weight by volume; ROD: Relative optical density; nm: Nanometer; SD: Standard deviation. How to cite this article Benjamin S, Roshni, Thomas SS, Nainan MT. Grape Seed Extract as a Potential Remineralizing Agent: A Comparative in vitro Study. J Contemp Dent Pract 2012;13(4):425-430.

Doxorubicin-loaded Fe3O4-ZIF-8 nano-composites for hepatocellular carcinoma therapy

2019 ◽  
Vol 33 (10) ◽  
pp. 1373-1381 ◽  
Author(s):  
Chong Cheng ◽  
Cheng Li ◽  
Xulong Zhu ◽  
Wei Han ◽  
Jianhui Li ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Hepatocellular Carcinoma ◽  
Cellular Uptake ◽  
Laser Scanning ◽  
Drug Loading ◽  
Confocal Laser Scanning Microscope ◽  
Confocal Laser ◽  
Nano Composites ◽  
High Drug ◽  
High Drug Loading

Hepatocellular carcinoma (HCC) is one of the most common and malignant cancers and has no effective therapeutic approaches. Chemotherapeutic drug doxorubicin (DOX) is widely used for HCC therapy, but its application is limited by the clinical toxicity. In the present study, an Fe3O4-ZIF-8 magnetic nano-composite was fabricated and used for DOX delivery for HCC therapy. The morphology, structure and property of Fe3O4-ZIF-8 nano-composites were evaluated by scanning electron microscopy, transmission electron microscopy and N2 adsorption-desorption isotherms studies. The drug release from DOX@Fe3O4-ZIF-8 was measured in pH 7.4 phosphate-buffered saline. The cellular uptake ability of DOX@Fe3O4-ZIF-8 into hepatocarcinoma cell line (MHCC97H) was visualized with a confocal laser scanning microscope. The effects of Fe3O4-ZIF-8, DOX and DOX@Fe3O4-ZIF-8 against MHCC97H cells were evaluated by CCK-8 assay and flow cytometry assay. Fe3O4-ZIF-8 nano-composites were synthesized and used as a nano-carrier for the delivery of DOX. Because of high drug loading property of ZIF-8, 1 mg Fe3O4-ZIF-8 nano-composites loaded 120 μg DOX when DOX@Fe3O4-ZIF-8 was synthesized in 30 mg/mL DOX solution. The cumulative DOX release curve showed a slow and sustained release pattern over time. The results of CCK-8 assay showed that Fe3O4-ZIF-8 was nontoxic to MHCC97H cells, and DOX@Fe3O4-ZIF-8 presented effective inhibiting effect on cell viability of MHCC97H cells. Cellular uptake assay showed that DOX@Fe3O4-ZIF-8 accumulated in both cytoplasm and nuclei. Moreover, because of valid drug accumulation, DOX@Fe3O4-ZIF-8 exhibited a good inducing effect on cell apoptosis of MHCC97H cells. In conclusion, based on the nontoxic and high drug loading capability of Fe3O4-ZIF-8, DOX@Fe3O4-ZIF-8 presented enhanced effects on HCC cells compared to free DOX, indicating its potential for the chemotherapy of HCC.

Polymeric Micelles Modified by Folate-PEG-Lipid for Targeted Drug Delivery to Cancer Cells In Vitro

2008 ◽  
Vol 8 (6) ◽  
pp. 3085-3090 ◽  
Author(s):  
Akihiro Hayama ◽  
Tatsuhiro Yamamoto ◽  
Masayuki Yokoyama ◽  
Kumi Kawano ◽  
Yoshiyuki Hattori ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Cellular Uptake ◽  
Laser Scanning ◽  
Polymeric Micelles ◽  
Folate Receptor ◽  
Drug Carrier ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
Kb Cells ◽  
Targeted Drug

A novel technique was developed for the formation of ligand-targeted polymeric micelles that can be applicable to various ligands. For tumor-specific drug delivery, camptothecin (CPT)-loaded polymeric micelles were modified by folate to produce a folate-receptor-targeted drug carrier. Folate-linked PEG5000-distearoylphosphatidylethanolamine (folate-PEG5000-DSPE) was added when preparations of drug-loaded polymeric micelles, resulting in folate ligands exposed to the surface. Folate-modified CPT-loaded polymeric micelles (F-micelle) were evaluated by measuring cellular uptake using a flow cytometer, fluorescence microscopy, and confocal laser scanning microscopy, and by cytotoxicity measurement. The results revealed that F-micelle showed higher cellular uptake in KB cells over-expressing folate receptor (FR) and higher cytotoxicity compared with non-folate modified CPT-loaded polymeric micelles (plain micelles) in KB cells, but not in FR-negative HepG2 cells. This result indicated that polymeric micelles were successfully modified by the folate-linked lipid.

scholarly journals Chlorin e6-Biotin Conjugates for Tumor-Targeting Photodynamic Therapy

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7342
Author(s):  
Wei Liu ◽  
Xingqun Ma ◽  
Yingying Jin ◽  
Jie Zhang ◽  
Yang Li ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Hela Cells ◽  
Tumor Targeting ◽  
Laser Scanning ◽  
Water Solubility ◽  
Laser Scanning Microscopy ◽  
Chlorin E6 ◽  
Confocal Laser ◽  
Oxygen Generation ◽  
Targeting Ability

To improve the tumor-targeting efficacy of photodynamic therapy, biotin was conjugated with chlorin e6 to develop a new tumor-targeting photosensitizer, Ce6-biotin. The Ce6-biotin had good water solubility and low aggregation. The singlet-oxygen generation rate of Ce6-biotin was slightly increased compared to Ce6. Flow cytometry and confocal laser scanning microscopy results confirmed Ce6-biotin had higher binding affinity toward biotin-receptor-positive HeLa human cervical carcinoma cells than its precursor, Ce6. Due to the BR-targeting ability of Ce6-biotin, it exhibited stronger cytotoxicity to HeLa cells upon laser irradiation. The IC50 against HeLa cells of Ce6-biotin and Ce6 were 1.28 µM and 2.31 µM, respectively. Furthermore, both Ce6-biotin and Ce6 showed minimal dark toxicity. The selectively enhanced therapeutic efficacy and low dark toxicity suggest that Ce6-biotin is a promising PS for BR-positive-tumor-targeting photodynamic therapy.

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