Synthesis of biocompatible nanocrystalline cellulose against folate receptors as a novel carrier for targeted delivery of doxorubicin

2021 ◽  
pp. 109731
Author(s):  
Ansar Karimian ◽  
Bahman Yousefi ◽  
Farzin Sadeghi ◽  
Farideh Feizi ◽  
Hossein Najafzadehvarzi ◽  
...  
Keyword(s):  
Targeted Delivery ◽  
Nanocrystalline Cellulose ◽  
Folate Receptors

scholarly journals Targeted delivery and enhanced gene-silencing activity of centrally modified folic acid–siRNA conjugates

2019 ◽  
Vol 48 (1) ◽  
pp. 75-85 ◽  
Author(s):  
Lidya Salim ◽  
Golam Islam ◽  
Jean-Paul Desaulniers
Keyword(s):  
Folic Acid ◽  
Gene Silencing ◽  
Cancer Cells ◽  
Targeted Delivery ◽  
Target Cells ◽  
Gene Target ◽  
Folate Receptors ◽  
Normal Tissues ◽  
Sense Strand ◽  
Low Cytotoxicity

Abstract One of the major hurdles in RNAi research has been the development of safe and effective delivery systems for siRNAs. Although various chemical modifications have been proposed to improve their pharmacokinetic behaviour, their delivery to target cells and tissues presents many challenges. In this work, we implemented a receptor-targeting strategy to selectively deliver siRNAs to cancer cells using folic acid as a ligand. Folic acid is capable of binding to cell-surface folate receptors with high affinity. These receptors have become important molecular targets for cancer research as they are overexpressed in numerous cancers despite being expressed at low levels in normal tissues. Employing a post-column copper-catalyzed alkyne–azide cycloaddition (CuAAC), we report the synthesis of siRNAs bearing folic acid modifications at different positions within the sense strand. In the absence of a transfection carrier, these siRNAs were selectively taken up by cancer cells expressing folate receptors. We show that centrally modified folic acid–siRNAs display enhanced gene-silencing activity against an exogenous gene target (∼80% knockdown after 0.75 μM treatment) and low cytotoxicity. In addition, these siRNAs achieved potent dose-dependent knockdown of endogenous Bcl-2, an important anti-apoptotic gene.

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.

Synthesis of a functionalized dipeptide for targeted delivery and pH-sensitive release of chemotherapeutics

2020 ◽  
Vol 56 (2) ◽  
pp. 285-288 ◽  
Author(s):  
Sonia Kiran ◽  
Pankaj Dwivedi ◽  
Renuka Khatik ◽  
Sadaf Hameed ◽  
Monika Dwivedi ◽  
...  
Keyword(s):  
Folic Acid ◽  
Targeted Delivery ◽  
Ph Sensitive ◽  
Folate Receptors ◽  
Peptide Nanoparticles

Design of pH-sensitive folic acid conjugated diphenyl peptide nanoparticles for targeted folate receptors mediated endocytosis.

In Vitro Studies of Prednisolone Loaded PLGA Nanoparticles-Surface Functionalized With Folic Acid on Glioma and Macrophage Cell Lines

2020 ◽  
Vol 27 (3) ◽  
pp. 407-417
Author(s):  
Sriprasad Acharya ◽  
Joyceline Praveena ◽  
Bharath Raja Guru
Keyword(s):  
Folic Acid ◽  
Block Copolymer ◽  
Cell Lines ◽  
Targeted Delivery ◽  
Inhibitory Effect ◽  
Free Drug ◽  
Growth Inhibitory Effect ◽  
Folate Receptors ◽  
Growth Inhibitory ◽  
Anti Inflammatory

Background: Glucocorticoids are employed for their anti-inflammatory effects in treatingglioma, whose cells are known to overexpress the folate receptors. Some glucocorticoids haveshown inhibitory effects, but the efficacy of prednisolone when delivered via folate receptormediateduptake, has not been attempted. The study aimed to assess the efficacy of targeteddelivery of prednisolone on glioma cell lines like C6 and U87 via the folate receptors. Methods: Targeted delivery of prednisolone was achieved by initially conjugating folic acid (FA)to the di-block copolymer of polylactic acid (PLA) – polyethylene glycol (PEG). This moietycarrying di-block copolymer was incorporated on the surface of the drug-loaded poly lactic-coglycolicacid (PLGA) nanoparticle (NP) by employing the Interfacial Activity Assisted SurfaceFunctionalization (IAASF) technique. The NPs were evaluated for size, zeta potential, and drugloading. It was characterized using particle size analyser, SEM, 1H-NMR, and XRD. cell uptake,cytotoxicity, and anti-inflammatory activities were studied for various formulations. Results: The cytotoxicity assay indicated a high cell growth inhibitory effect of drug encapsulatedNPs with FA moiety as compared to free drug and NPs without the moiety for an incubationperiod of three, five, and six days. The growth-inhibitory effect of the free drug was short-lived,whereas FA functionalized NPs showed higher uptake and sustained inhibitory effect, and werealso able to significantly control the release of pro-inflammatory cytokines like tumour necrosisfactor-alpha (TNF-α) and nitric oxide (NO). Conclusion: Uptake, attenuation of pro-inflammatory signals, and the inhibitory effect ofprednisolone on the cells were more effective when targeted with the FA moiety on the surfaceof NPs as compared to free drug and NPs without the moiety.

scholarly journals The Overexpression of Folate Receptors in Gynecologic Oncology - a Diagnostic and Therapeutic Approach

2020 ◽  
Vol 70 (12) ◽  
pp. 4532-4536
Keyword(s):  
Cervical Cancer ◽  
Targeted Delivery ◽  
Folate Receptor ◽  
Gynecologic Oncology ◽  
Cervical Dysplasia ◽  
High Sensitivity ◽  
Apical Surface ◽  
Epithelial Tumor ◽  
Folate Receptors ◽  
Epithelial Origin

Since the discovery of the overexpression of alpha folate receptors (α-FR) in different types of epithelial origin cancers, the arising implications in diagnosis, prognosis and therapy have been thoroughly studied. The α-FR is a glycosylphosphatidylinositol-anchored protein with high affinity for 5-methyltetrahydrofolate, the predominant plasma folate. The expression of FRα in healthy cells is found to be only on the apical surface, but the expression in numerous carcinomas of epithelial origin is 100-300 times higher than on healthy cells and it is in the order of 1-10 million receptor copies per cell. Due to the increased expression of α-FR in epithelial tumor cells, it has been emphasized that this receptor could represent a useful target for the development of new and selective anticancer drugs. For targeted delivery to FR expressing cells, it is involved the covalent linkage of folate to a variety of molecules, including chemotherapy or imaging agents. Exploiting the overexpression of α-FR in cervical dysplasia and cervical cancer, a new, cost effective and high sensitivity screening test has been developed. Keywords: folate receptor, gynecologic oncology, folate receptor-mediated staining procedures, cervical cancer screening

scholarly journals Quantum dots as targeted doxorubicin drug delivery nanosystems in human lung cancer cells

2020 ◽  
Author(s):  
Monika Ruzycka ◽  
Patrycja Kowalik ◽  
Agata Kowalczyk ◽  
Piotr Bujak ◽  
Anna M. Nowicka ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Delivery ◽  
Quantum Dots ◽  
Cancer Cells ◽  
Targeted Delivery ◽  
A549 Cells ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Dna Breaks ◽  
Folate Receptors

Abstract Background Lung cancer is one of the most frequently diagnosed cancer all over the world and a leading cancer-related mortality. The therapy of lung cancer includes surgery, chemotherapy and radiatherapy and mailny depends on the type and stage of lung cancer characterized based on WHO guidelines. Althought the conventional chemotherapy is the main treatment option for small cell lung cancer (SCLC) and a common treatment for non-SCLC it is characterized with lack of specificity resulting to severe toxicities of normal cells and harmful side effects. Therefore, targeted drug delivery (TDD) systems have been used to reduce the systemic toxicity of some conventional chemotherapies in lung cancer. Quantum dots (QDs) are fascinating nanoscale crystals that can serve as nanocarriers in TDD due to their unique physicochemical properties. Therefore, in this paper, the as-desiged QDs, Ag-In-Zn-S-based nanoconjugates for selective doxorubicin (DOX) targeting to lung cancer cells were developed. The QD nanocrystals were modified with 11-mercaptoundecanoic acid (MUA), L-cysteine (Cys) and lipoic acid (LA) used as drug carriers for targeted delivery of DOX to A549 cells through conjugated folic acid (FA) a self-navigation molecule that docks to the folate receptors on cancer cells. The comprechensive physicochemical, cytotoxicity and genotoxicity studies were performed to characterise the novel QD-based nanocaries and their anticancer cargos. Results The results from FTIR, DLS and fluorescence quenching evidenced the successful attachment of FA to the QDs nanocrystals and DOX to the QDs-FA nanocarriers. UV-vis analysis determined the amount of FA and DOX covalently anchored to the QDs nanocrystal surface. Biological screeining revealed that QDs-FA-DOX nanoconjugates showed higher cytotoxicity in comparison to other forms of the synthesized QD samples, suggesting the cytotoxic effect of liberated DOX from the QD constructs. QD-MUA-FA-DOX occurred to be the most cytotoxic against A549 cells among nanoconjugates. In vitro scratch assay also revealed significant inhibition of A549 migration only due to treatment with QD-MUA-FA-DOX. Studies evidenced that all the nanoconjugates at IC 50 induced significantly more DNA breaks than that observed in non-treated cells. All in all, significant and the greatest cytotoxicity, genotoxicity together with inhibition of migratory potential of A549 cells was observed for QD-MUA-FA-DOX. Conclusion The studies show the therapeutic efficacy of DOX-loaded QD-based cargos suggesting their promising role as novel drug delivery systems navigating to folate receptors in lung cancer cells.

scholarly journals Targeting Cancer Cells Overexpressing Folate Receptors with New Terpolymer-Based Nanocapsules: Toward a Novel Targeted DNA Delivery System for Cancer Therapy

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1275
Author(s):  
Elena Bellotti ◽  
Maria Grazia Cascone ◽  
Niccoletta Barbani ◽  
Daniela Rossin ◽  
Raffaella Rastaldo ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Cancer Cells ◽  
Targeted Delivery ◽  
Genetic Material ◽  
Cell Uptake ◽  
Target Cells ◽  
Folate Receptors ◽  
Good Ability ◽  
Wide Range ◽  
Target Effects

Chemotherapeutics represent the standard treatment for a wide range of cancers. However, these agents also affect healthy cells, thus leading to severe off-target effects. Given the non-selectivity of the commonly used drugs, any increase in the selective tumor tissue uptake would represent a significant improvement in cancer therapy. Recently, the use of gene therapy to completely remove the lesion and avoid the toxicity of chemotherapeutics has become a tendency in oncotherapy. Ideally, the genetic material must be safely transferred from the site of administration to the target cells, without involving healthy tissues. This can be achieved by encapsulating genes into non-viral carriers and modifying their surface with ligands with high selectivity and affinity for a relevant receptor on the target cells. Hence, in this work we evaluate the use of terpolymer-based nanocapsules for the targeted delivery of DNA toward cancer cells. The surface of the nanocapsules is decorated with folic acid to actively target the folate receptors overexpressed on a variety of cancer cells. The nanocapsules demonstrate a good ability of encapsulating and releasing DNA. Moreover, the presence of the targeting moieties on the surface of the nanocapsules favors cell uptake, opening up the possibility of more effective therapies.

pH Dependent Release Potential of Natural Polymers in Sustained Release of Ornidazole From Colon Targeted Delivery System)

2019 ◽  
Vol 9 (02) ◽  
Author(s):  
Sharma Pankaj ◽  
Tailang Mukul
Keyword(s):  
Drug Release ◽  
Delivery System ◽  
Targeted Delivery ◽  
Guar Gum ◽  
Acidic Environment ◽  
Natural Polymers ◽  
Weight Variation ◽  
Curve Determination ◽  
Preformulation Studies

The aim of present work was to prepare colon specific delivery system of Ornidazole using different ratio of shellac, zein and guar gum. From study of various literature it revealed that shellac, zein and guar gum released drug from dosage form at the pH of 6.9, 11.5, 7-9 respectively. The main problem associated with colon targeted drug delivery system is degradation of drug in the acidic environment of stomach to circumvent the present problem different combinations of shellac, zein and guar gum were employed in the formulation of colon targeted tablet. Several preformulation parameters were determined such as melting point, FTIR spectroscopy, preparation of calibration curve, determination of λmax and partition coefficient. After the preformulation studies, next steps were preparation of core tablets, evaluation of core of tablets and coating of tablets. The data obtained from preformulation study seven formulations were developed and evaluated for various parameters. Based on evaluated parameter such as weight variation, friability, dissolution study, invitro drug release etc. the F7 formulation show better results colon targeted tablets. Drug content in F7 formulation was 95% and drug release after 6 hrs was 96%. Formulation containing combination of shellac, zein and guar gum released least amount of drug in the acidic environment of stomach and released most of the drug in colon. It is evide

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