ENHANCING DELIVERY OF GADOLINIUM-LOADED, TARGETED NANOPARTICLES: EFFECT OF STERIC HINDRANCE ON FOLATE RECEPTOR-MEDIATED CELLULAR UPTAKE IN VITRO

2014 ◽  
Vol 30 (10) ◽  
pp. S217
Author(s):  
C.D. Sarsons ◽  
A.L. Doiron ◽  
H.I. Labouta ◽  
R.D. Shepherd ◽  
L.B. Andersen ◽  
...  
Keyword(s):  
Cellular Uptake ◽  
Steric Hindrance ◽  
Folate Receptor ◽  
Targeted Nanoparticles

scholarly journals Folate Receptor-Targeting and Reactive Oxygen Species-Responsive Liposomal Formulation of Methotrexate for Treatment of Rheumatoid Arthritis

Pharmaceutics ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 582 ◽  
Author(s):  
Chen ◽  
Amerigos J.C. ◽  
Su ◽  
Guissi ◽  
Xiao ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Reactive Oxygen Species ◽  
Hydrogen Peroxide ◽  
Drug Release ◽  
Cellular Uptake ◽  
Folate Receptor ◽  
Oxygen Species ◽  
Activated Macrophages

Multifunctional nanomedicines with active targeting and stimuli-responsive drug release function utilizing pathophysiological features of the disease are regarded as an effective strategy for treatment of rheumatoid arthritis (RA). Under the inflammatory environment of RA, activated macrophages revealed increased expression of folate receptor and elevated intracellular reactive oxygen species (ROS) level. In this study, we successfully conjugated folate to polyethylene glycol 100 monostearate as film-forming material and further prepared methotrexate (MTX) and catalase (CAT) co-encapsulated liposomes, herein, shortened to FOL-MTX&CAT-L, that could actively target to activated macrophages. Thereafter, elevated intracellular hydrogen peroxide, the main source of ROS, diffused into liposomes and encapsulated CAT catalyzed the decomposition of hydrogen peroxide into oxygen and water. Continuous oxygen-generation inside liposomes would eventually disorganize its structure and release the encapsulated MTX. We characterized the in vitro drug release, cellular uptake and cytotoxicity studies as well as in vivo pharmacokinetics, biodistribution, therapeutic efficacy and safety studies of FOL-MTX&CAT-L. In vitro results revealed that FOL-MTX&CAT-L possessed sufficient ROS-sensitive drug release, displayed an improved cellular uptake through folate-mediated endocytosis and exhibited a higher cytotoxic effect on activated RAW264.7 cells. Moreover, in vivo results showed prolonged blood circulation time of PEGylated liposomes, enhanced accumulation of MTX in inflamed joints of collagen-induced arthritis (CIA) mice, reinforced therapeutic efficacy and minimal toxicity toward major organs. These results imply that FOL-MTX&CAT-L may be used as an effective nanomedicine system for RA treatment.

Synthesis and In Vitro Evaluation of Defined HPMA Folate Conjugates: Influence of Aggregation on Folate Receptor (FR) Mediated Cellular Uptake

2010 ◽  
Vol 11 (9) ◽  
pp. 2274-2282 ◽  
Author(s):  
Matthias Barz ◽  
Fabiana Canal ◽  
Kaloian Koynov ◽  
R. Zentel ◽  
María J. Vicent
Keyword(s):  
Cellular Uptake ◽  
Folate Receptor ◽  
In Vitro Evaluation

In Vitro and In Vivo Evaluation of Novel DTX-Loaded Multifunctional Heparin-Based Polymeric Micelles Targeting Folate Receptors and Endosomes

2020 ◽  
Vol 15 (4) ◽  
pp. 341-359
Author(s):  
Moloud Kazemi ◽  
Jaber Emami ◽  
Farshid Hasanzadeh ◽  
Mohsen Minaiyan ◽  
Mina Mirian ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Antitumor Activity ◽  
Cellular Uptake ◽  
Folate Receptor ◽  
Chemotherapeutic Agents ◽  
Water Soluble ◽  
Growth Monitoring ◽  
Tumor Bearing

Background: The development of biocompatible tumor-targeting delivery systems for anticancer agents is essential for efficacious cancer chemotherapy. Nanoparticles, as drug delivery cargoes for cancer therapy, are rapidly improving to overcome the limitations of conventional chemotherapeutic agents. Heparin–modified nanoparticles are currently being considered as one of the favorable carriers for the delivery of chemotherapeutics to cancer tissues. Objective: This study was aimed at evaluating the in vitro and in vivo antitumor activity of a novel targeted, pH-sensitive, heparin-based polymeric micelle loaded with the poorly water-soluble anticancer drug, docetaxel (DTX). The micelles could overcome the limited water solubility, non-specific distribution, and insufficient drug concentration in tumor tissues. Methods: DTX-loaded folate targeted micelles were prepared and evaluated for physicochemical properties, drug release, in vitro cellular uptake and cytotoxicity in folate receptor-positive and folate receptor-negative cells. Furthermore, the antitumor activity of DTX-loaded micelles was evaluated in the tumor-bearing mice. Some related patents were also studied in this research. Results: The heparin-based targeted micelles exhibited higher in vitro cellular uptake and cytotoxicity against folate receptor over-expressed cells due to the specific receptor-mediated endocytosis. DTX-loaded micelles displayed greater antitumor activity, higher anti-angiogenesis effects, and lower systemic toxicity compared with free DTX in a tumor-induced mice model as confirmed by tumor growth monitoring, immunohistochemical evaluation, and body weight shift. DTX-loaded targeting micelles demonstrated no considerable toxicity on major organs of tumor-bearing mice compared with free DTX. Conclusion: Our results indicated that DTX-loaded multifunctional heparin-based micelles with desirable antitumor activity and low toxicity possess great potential as a targeted drug delivery system in the treatment of cancer.

scholarly journals Preparation and Characterization of Novel Perfluorooctyl Bromide Nanoparticle as Ultrasound Contrast Agent via Layer-by-Layer Self-Assembly for Folate-Receptor-Mediated Tumor Imaging

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Yue Hu ◽  
Yong Wang ◽  
Jianshuai Jiang ◽  
Baosan Han ◽  
Shengmin Zhang ◽  
...  
Keyword(s):  
Ultrasound Imaging ◽  
Self Assembly ◽  
Folate Receptor ◽  
Layer By Layer ◽  
The Novel ◽  
Chitosan Derivative ◽  
Glycol Chitosan ◽  
Targeted Nanoparticles ◽  
Perfluorooctyl Bromide

A folate-polyethylene glycol-chitosan derivative was synthesized and its structure was characterized. An optimal perfluorooctyl bromide nanocore template was obtained via utilizing the ultrasonic emulsification method combining with orthogonal design. The targeted nanoparticles containing targeted shell of folate-polyethylene glycol-chitosan derivative and perfluorooctyl bromide nanocore template of ultrasound imaging were prepared successfully by exploiting layer-by-layer self-assembly as contrast agent for ultrasound. Properties of the novel perfluorooctyl bromide nanoparticle were extensively studied by Dynamic Light Scattering and Transmission Electron Microscopy. The targeted nanoparticle diameter, polydispersity, and zeta potential are around 229.5 nm, 0.205, and44.7±0.6 mV, respectively. The study revealed that spherical core-shell morphology was preserved. Excellent stability of targeted nanoparticle is evidenced by two weeks of room temperature stability tests. The results of the cell viability assay and the hemolysis test confirmed that the targeted nanoparticle has an excellent biocompatibility for using in cell studies and ultrasound imaging in vivo. Most importantly, in vitro cell experiments demonstrated that an increased amount of targeted nanoparticles was accumulated in hepatocellular carcinoma cell line Bel7402 relative to hepatoma cell line L02. And targeted nanoparticles had also shown better ultrasound imaging abilities in vitro. The data suggest that the novel targeted nanoparticle may be applicable to ultrasonic molecular imaging of folate-receptor overexpressed tumor.

scholarly journals Development of Folate-Functionalized PEGylated Zein Nanoparticles for Ligand-Directed Delivery of Paclitaxel

Pharmaceutics ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 562 ◽  
Author(s):  
Zar Chi Soe ◽  
Wenquan Ou ◽  
Milan Gautam ◽  
Kishwor Poudel ◽  
Bo Kyun Kim ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Targeted Delivery ◽  
Folate Receptor ◽  
A549 Cells ◽  
Kb Cells ◽  
Cell Cycle Profile ◽  
Folate Receptors ◽  
Targeted Nanoparticles ◽  
Nanoparticle System

In this study, we investigated the active targeted delivery of a hydrophobic drug, paclitaxel (PTX), via receptor-mediated endocytosis by folate receptors expressed on cancer cells using a protein-based nanoparticle system. PTX was loaded on zein nanoparticles and conjugated with folate (PTX/Zein-FA) to estimate its chemotherapeutic efficacy in folate receptor-expressing KB cancer cells. PTX/Zein-FA nanoparticles were successfully developed, with a nanoparticle size of ~180 nm and narrow polydispersity index (~0.22). Accelerated release of PTX in an acidic environment was observed for PTX/Zein-FA. An in vitro cellular study of PTX/Zein-FAs in KB cells suggested that PTX/Zein-FA improved the cytotoxic activity of PTX on folate receptors overexpressed in cancer cells by inducing proapoptotic proteins and inhibiting anti-apoptotic proteins. In addition, PTX/Zein-FA exhibited anti-migratory properties and could alter the cell cycle profile of KB cells. A549 cells, which are folate receptor-negative cancer cells, showed no significant enhancement in the in vitro cellular activities of PTX/Zein-FA. We describe the antitumor efficacy of PTX/Zein-FA in KB tumor-bearing mice with minimum toxicity in healthy organs, and the results were confirmed in comparison with free drug and non-targeted nanoparticles.

scholarly journals Lipid-polymer hybrid nanoparticles carrying doxorubicin and edelfosine combo for synergistic anticancer effect against drug-resistant Osteosarcoma

2020 ◽  
Author(s):  
Ping Yang ◽  
Lian Zhang ◽  
Tian Wang ◽  
Qi Liu ◽  
Jing Wang ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Folate Receptor ◽  
Drug Loading ◽  
Hybrid Nanoparticles ◽  
Anticancer Efficacy ◽  
Targeted Nanoparticles ◽  
Polymer Hybrid ◽  
Multiple Drugs

Abstract In this study, we have prepared a novel folate receptor-targeted doxorubicin (DOX) and edelfosine (ET)-loaded lipid polymer hybrid nanoparticle to enhance the anticancer efficacy in osteosarcoma. The dual-drug loaded nanoparticles showed a nanosized morphology and physiological stability. The targeted nanoparticles showed enhanced cellular internalization and subcellular distribution in MG63 cancer cells compared to that of non-targeted nanoparticles. Among many ratios of DOX and ET, 1:1 ratiometric combinations of drugs were observed to be highly synergistic in killing the cancer cells. MTT assay and caspase-3/7 activity assay clearly showed the superior anticancer efficacy of DE-FPLN formulations in inducing the cancer cell death. In vitro results indicate that the co-administration of two drugs in a folic acid-targeted nanoparticle could potentially induce the apoptosis and cell death. In vivo results displayed the potency of tumor cell killing and significant suppression of tumor growth without any detectable side effects. The lipid polymer hybrid nanocarriers with multiple properties of high drug loading, sequential and ratiometric drug release, improved physiological stability, prolonged blood circulation, and tumor-specific targeting are promising for the delivery of multiple drugs in the treatment of osteosarcoma.

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.

Using FRET to Measure the Time it Takes for a Cell to Destroy a Virus

2019 ◽  
Author(s):  
Candace E. Benjamin ◽  
Zhuo Chen ◽  
Olivia Brohlin ◽  
Hamilton Lee ◽  
Stefanie Boyd ◽  
...  
Keyword(s):  
Cellular Uptake ◽  
Rhodamine B ◽  
Virus Like Particle ◽  
A Cell ◽  
Viral Nanoparticles ◽  
The Stability ◽  
Open Question ◽  
Viral Surface ◽  
Fret Pair

<div><div><div><p>The emergence of viral nanotechnology over the preceding two decades has created a number of intellectually captivating possible translational applications; however, the in vitro fate of the viral nanoparticles in cells remains an open question. Herein, we investigate the stability and lifetime of virus-like particle (VLP) Qβ - a representative and popular VLP for several applications - following cellular uptake. By exploiting the available functional handles on the viral surface, we have orthogonally installed the known FRET pair, FITC and Rhodamine B, to gain insight of the particle’s behavior in vitro. Based on these data, we believe VLPs undergo aggregation in addition to the anticipated proteolysis within a few hours of cellular uptake.</p></div></div></div>

Recent Advances in Curcumin Nanocarriers for the Treatment of Different Types of Cancer with Special Emphasis on In Vitro Cytotoxicity and Cellular Uptake Studies

2020 ◽  
Vol 10 (5) ◽  
pp. 577-590
Author(s):  
Jai B. Sharma ◽  
Shailendra Bhatt ◽  
Asmita Sharma ◽  
Manish Kumar
Keyword(s):  
Cancer Cells ◽  
Cellular Uptake ◽  
Anticancer Agents ◽  
Targeted Delivery ◽  
In Vitro Cytotoxicity ◽  
Curcumin Nanoparticles ◽  
Cytotoxicity Studies ◽  
Delivery Technique ◽  
Different Types

Background: The potential use of nanocarriers is being explored rapidly for the targeted delivery of anticancer agents. Curcumin is a natural polyphenolic compound obtained from rhizomes of turmeric, belongs to family Zingiberaceae. It possesses chemopreventive and chemotherapeutic activity with low toxicity in almost all types of cancer. The low solubility and bioavailability of curcumin make it unable to use for the clinical purpose. The necessity of an effective strategy to overcome the limitations of curcumin is responsible for the development of its nanocarriers. Objective: This study is aimed to review the role of curcumin nanocarriers for the treatment of cancer with special emphasis on cellular uptake and in vitro cytotoxicity studies. In addition to this, the effect of various ligand conjugated curcumin nanoparticles on different types of cancer was also studied. Methods: A systematic review was conducted by extensively surfing the PubMed, science direct and other portals to get the latest update on recent development in nanocarriers of curcumin. Results: The current data from recent studies showed that nanocarriers of curcumin resulted in the targeted delivery, higher efficacy, enhanced bioavailability and lower toxicity. The curcumin nanoparticles showed significant inhibitory effects on cancer cells as compared to free curcumin. Conclusion: It can be concluded that bioavailability of curcumin and its cytotoxic effect to cancer cells can be enhanced by the development of curcumin based nanocarriers and it was found to be a potential drug delivery technique for the treatment of cancer.

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