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.

Preparation and In Vitro Cellular Uptake Assessment of Multifunctional Rubik-Like Magnetic Nano-Assemblies

2019 ◽  
Vol 19 (6) ◽  
pp. 3301-3309
Author(s):  
Xiawen Zheng ◽  
Yuejian Chen ◽  
Zhiming Wang ◽  
Lina Song ◽  
Yu Zhang ◽  
...  
Keyword(s):  
Oleic Acid ◽  
Folic Acid ◽  
Cellular Uptake ◽  
Hela Cells ◽  
Drug Loading ◽  
Superparamagnetic Iron Oxide ◽  
Drug Carriers ◽  
High Drug ◽  
High Drug Loading

Through self-assembly of nanoparticles into high-order and stable structures of cubic clusters, high drug-loading rubik-like magnetic nano-assemblies (MNAs), possessing folic acid targeting and strong magnetism-enhanced cellular uptake capabilities, were built. In this study, the core of the cubic drug assemblies consisted of four monodisperse superparamagnetic iron oxide nanoparticles coated with layers of oleic acid (Fe3O4@OA), simultaneously encapsulating fluorescein, and Paclitaxol (Flu-MNAs and PTX-MNAs) for imaging and therapeutic applications. To enable preferential tumor cellular uptake by the nanocarriers, the outermost layer of Fe3O4 was functionalized with the new dual-oleic acid-polyethylene glycol-folic acid polymer (FA-PEG-Lys-OA2) as a “shell.” The drug carriers exhibited excellent stability and biocompatibility, and showed high drug loading and excellent magnetic response In Vitro. Furthermore, preliminary evaluations of the drug carriers with Hela cells showed effective cellular targeting capability. In addition, the cubic assemblies enhanced anticancer efficiency for Hela cells compared to bare drugs. Especially, the applied external magnetic field further improved the uptake of the vectors, and thereby enhanced the inhibitory effect. In brief, all these results suggested that cubic assemblies could serve as potential strategies for targeted anticancer therapies.

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.

Dimeric camptothecin-loaded RGD-modified targeted cationic polypeptide-based micelles with high drug loading capacity and redox-responsive drug release capability

2017 ◽  
Vol 5 (12) ◽  
pp. 2501-2510 ◽  
Author(s):  
Zhaopei Guo ◽  
Xingzhi Zhou ◽  
Mengze Xu ◽  
Huayu Tian ◽  
Xuesi Chen ◽  
...  
Keyword(s):  
Drug Release ◽  
Cellular Uptake ◽  
Cell Apoptosis ◽  
Drug Loading ◽  
Loading Capacity ◽  
High Drug ◽  
Redox Responsive ◽  
High Drug Loading

Dimeric CPT (DCPT) could be largely encapsulated in polypeptide micelle RGD-PEG-g-PLL-b-PLeu (DRPPP) with redox-sensitive drug release capability, showing remarkable cellular uptakeviaRGD targeting, enhanced cytotoxicity and cell apoptosis.

scholarly journals In-vitro study of formulation and evaluation of nanosuspension of tamoxifen

2018 ◽  
Vol 7 (5) ◽  
pp. 926
Author(s):  
Somasekhar M. Reddy ◽  
Navispaul N. Sriganth ◽  
Chandra S. Kumar ◽  
Santosh C. Gursale ◽  
Vijay V. Ragavan
Keyword(s):  
Electron Microscopy ◽  
Particle Size ◽  
Size Distribution ◽  
Drug Loading ◽  
Polarized Light ◽  
Scanning Calorimetry ◽  
High Drug ◽  
Dissolution Properties ◽  
High Drug Loading

Background: Nanosuspension technology has been developed as a promising candidate for efficient delivery of hydrophobic drugs. It could maintain the required crystalline state of the drug with reduced particle size, leading to an increased reporting on dissolution rate and therefore improved bioavailability.Methods: In this paper, we report on the preparation of Tamoxifen nanosuspension by high-pressure homogenization (HPH). The aim is to obtain a stable nanosuspension with an increased drug saturation solubility and dissolution velocity. The morphology and particle size distribution of the modified nanosuspensions were characterized by the means of several analyses that included: transmission electron microscopy (TEM), polarized light microscopy (PLM), scanning electron microscopy, differential scanning calorimetry (DSC) and powder X- ray diffractometry (XRD).Results: HPH was employed to produce aqueous drug nanosuspensions with fine solubility and dissolution properties, which render the produced particles stable up to one month. In addition, the prepared nanosuspensions possessed a high drug-loading efficiency (10%). The recoded zeta potential values (≈ -27 mV) indicated that the prepared nanosuspensions possess a higher degree of long-term stability. TEM data showed narrow size distribution with average size 322.7 nm. Morphologically, as indicated from results, the produced nanosuspensions have a homogenous distribution even after redispersion, indicating the stability of the product.Conclusions: It was possible to obtain Tamoxifen nanosuspensions with fine solubility and dissolution properties. Nanosuspensions possessed a high drug- loading (10%), which could reduce the dosage administration and gastrointestinal side effects. HPH can be employed to produce aqueous drug nanosuspensions that are stable up to one month. Aqueous nanosuspension can be converted to dry nanocrystals by lyophilization which offer superior physicochemical properties.

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.

scholarly journals Photosensitive Supramolecular Micelle-Mediated Cellular Uptake of Anticancer Drugs Enhances the Efficiency of Chemotherapy

2020 ◽  
Vol 21 (13) ◽  
pp. 4677 ◽  
Author(s):  
Yihalem Abebe Alemayehu ◽  
Wen-Lu Fan ◽  
Fasih Bintang Ilhami ◽  
Chih-Wei Chiu ◽  
Duu-Jong Lee ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Anticancer Drugs ◽  
Cellular Uptake ◽  
Self Assembly ◽  
Apoptotic Cell ◽  
Drug Loading ◽  
Stimuli Responsive ◽  
High Drug ◽  
High Drug Loading

The development of stimuli-responsive supramolecular micelles with high drug-loading contents that specifically induce significant levels of apoptosis in cancer cells remains challenging. Herein, we report photosensitive uracil-functionalized supramolecular micelles that spontaneously form via self-assembly in aqueous solution, exhibit sensitive photo-responsive behavior, and effectively encapsulate anticancer drugs at high drug-loading contents. Cellular uptake analysis and double-staining flow cytometric assays confirmed the presence of photo-dimerized uracil groups within the irradiated micelles remarkably enhanced endocytic uptake of the micelles by cancer cells and subsequently led to higher levels of apoptotic cell death, and thus improved the therapeutic effect in vitro. Thus, photo-dimerized uracil-functionalized supramolecular micelles may potentially represent an intelligent nanovehicle to improve the safety, efficacy, and applicability of cancer chemotherapy, and could also enable the development of nucleobase-based supramolecular micelles for multifunctional biomaterials and novel biomedical applications.

3-D imaging of cells using a confocal laser scanning microscope and digital image processing

1988 ◽  
Vol 46 ◽  
pp. 96-97
Author(s):  
Thomas M. Jovin ◽  
Michel Robert-Nicoud ◽  
Donna J. Arndt-Jovin ◽  
Thorsten Schormann
Keyword(s):  
Laser Scanning ◽  
Confocal Laser Scanning Microscope ◽  
Laser Scanning Microscopy ◽  
Confocal Laser Scanning ◽  
Confocal Laser ◽  
Scanning Microscope ◽  
Laser Scanning Microscope ◽  
Biochemical Processes ◽  
Adjacent Structures

Light microscopic techniques for visualizing biomolecules and biochemical processes in situ have become indispensable in studies concerning the structural organization of supramolecular assemblies in cells and of processes during the cell cycle, transformation, differentiation, and development. Confocal laser scanning microscopy offers a number of advantages for the in situ localization and quantitation of fluorescence labeled targets and probes: (i) rejection of interfering signals emanating from out-of-focus and adjacent structures, allowing the “optical sectioning” of the specimen and 3-D reconstruction without time consuming deconvolution; (ii) increased spatial resolution; (iii) electronic control of contrast and magnification; (iv) simultanous imaging of the specimen by optical phenomena based on incident, scattered, emitted, and transmitted light; and (v) simultanous use of different fluorescent probes and types of detectors.We currently use a confocal laser scanning microscope CLSM (Zeiss, Oberkochen) equipped with 3-laser excitation (u.v - visible) and confocal optics in the fluorescence mode, as well as a computer-controlled X-Y-Z scanning stage with 0.1 μ resolution.

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