scholarly journals Methotrexate Gold Nanocarriers: Loading and Release Study. Its Activity in Colon and Lung Cancer Cells

2020 ◽  
Author(s):  
Beatriz Álvarez-González ◽  
Marisa Rozalen ◽  
María Fernández-Perales ◽  
Miguel A. Álvarez ◽  
Manuel Sánchez-Polo
Keyword(s):  
Cancer Cells ◽  
Folate Receptor ◽  
Ph Gradients ◽  
Cytotoxic Effects ◽  
Folate Receptors ◽  
Tumor Microenvironments ◽  
Drug Concentrations ◽  
Characterization Study ◽  
Specific Uptake ◽  
Dose Response Effect

In the present study the synthesis of gold nanoparticles (AuNPs) loaded with methotrexate (MTX) has been carried out in order to obtain controlled size and monodispersed nanocarriers, around 20nm. Characterization study shows metallic AuNPs with MTX polydispersed on the surface. MTX is linked by a replacement of citrate by the MTX carboxyl group. The drug release profiles showed faster MTX release when it is conjugated, which leads to the best control of plasma concentration. Also, the enhanced release observed at pH 5 could take advantage of the pH gradients that exist in tumor microenvironments to achieve high local drug concentrations. AuNPs-MTX conjugates were tested by flow cytometry against lung (A-549) and colon (HTC-116) cancer cell lines. Results for A-549 showed a lighter dose-response effect than for colon cancer ones. This could be related to the presence of folate receptors in line HTC-116 on the contrary than line A-549, supporting the specific uptake of folate-conjugated AuNPs-MTX by folate receptor positive tumor cells. Conjugates exhibited considerably higher cytotoxic effects compared with the effects of equal doses of free MTX. Anexin V-PI test sustain as cell death mechanism apoptosis, which is normally disabled in cancer cells.

scholarly journals Methotrexate Gold Nanocarriers: Loading and Release Study: Its Activity in Colon and Lung Cancer Cells

Molecules ◽  
2020 ◽  
Vol 25 (24) ◽  
pp. 6049
Author(s):  
Beatriz Álvarez-González ◽  
Marisa Rozalen ◽  
María Fernández-Perales ◽  
Miguel A. Álvarez ◽  
Manuel Sánchez-Polo
Keyword(s):  
Cancer Cells ◽  
Folate Receptor ◽  
Annexin V ◽  
Ph Gradients ◽  
Tumor Microenvironments ◽  
Drug Concentrations ◽  
Characterization Study ◽  
Specific Uptake ◽  
Dose Response Effect ◽  
20 Nm

In the present study, the synthesis of gold nanoparticles (AuNPs) loaded with methotrexate (MTX) has been carried out in order to obtain controlled size and monodispersed nanocarriers of around 20 nm. The characterization study shows metallic AuNPs with MTX polydispersed on the surface. MTX is linked by the replacement of citrate by the MTX carboxyl group. The drug release profiles show faster MTX release when it is conjugated, which leads to the best control of plasma concentration. Moreover, the enhanced release observed at pH 5 could take advantage of the pH gradients that exist in tumor microenvironments to achieve high local drug concentrations. AuNP–MTX conjugates were tested by flow cytometry against lung (A-549) and colon (HTC-116) cancer cell lines. Results for A-549 showed a weaker dose–response effect than for colon cancer ones. This could be related to the presence of folate receptors in line HTC-116 in comparison to line A-549, supporting the specific uptake of folate-conjugated AuNP–MTX by folate receptor positive tumor cells. Conjugates exhibited considerably higher cytotoxic effects compared with the effects of equal doses of free MTX. Annexin V-PI tests sustained the cell death mechanism of apoptosis, which is normally disabled in cancer cells.

scholarly journals A Novel Method of Magnetic Nanoparticles Functionalized with Anti-Folate Receptor Antibody and Methotrexate for Antibody Mediated Targeted Drug Delivery

Molecules ◽  
2022 ◽  
Vol 27 (1) ◽  
pp. 261
Author(s):  
Madeeha Shahzad Lodhi ◽  
Fatima Khalid ◽  
Muhammad Tahir Khan ◽  
Zahoor Qadir Samra ◽  
Shabbir Muhammad ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Magnetic Nanoparticles ◽  
Cancer Cells ◽  
Hela Cells ◽  
Targeted Drug Delivery ◽  
Folate Receptor ◽  
Enzyme Linked Immunosorbent Assay ◽  
Folate Receptors ◽  
Receptor Antibody ◽  
Targeted Drug

Therapeutic effects of anticancer medicines can be improved by targeting the specific receptors on cancer cells. Folate receptor (FR) targeting with antibody (Ab) is an effective tool to deliver anticancer drugs to the cancer cell. In this research project, a novel formulation of targeting drug delivery was designed, and its anticancer effects were analyzed. Folic acid-conjugated magnetic nanoparticles (MNPs) were used for the purification of folate receptors through a novel magnetic affinity purification method. Antibodies against the folate receptors and methotrexate (MTX) were developed and characterized with enzyme-linked immunosorbent assay and Western blot. Targeting nanomedicines (MNP-MTX-FR Ab) were synthesized by engineering the MNP with methotrexate and anti-folate receptor antibody (anti-FR Ab). The cytotoxicity of nanomedicines on HeLa cells was analyzed by calculating the % age cell viability. A fluorescent study was performed with HeLa cells and tumor tissue sections to analyze the binding efficacy and intracellular tracking of synthesized nanomedicines. MNP-MTX-FR Ab demonstrated good cytotoxicity along all the nanocomposites, which confirms that the antibody-coated medicine possesses the potential affinity to destroy cancer cells in the targeted drug delivery process. Immunohistochemical approaches and fluorescent study further confirmed their uptake by FRs on the tumor cells’ surface in antibody-mediated endocytosis. The current approach is a useful addition to targeted drug delivery for better management of cancer therapy along with immunotherapy in the future.

scholarly journals Exploiting the Efficacy of Tyro3 and Folate Receptors to Enhance the Delivery of Gold Nanoparticles into Colorectal Cancer Cells In Vitro

2020 ◽  
Author(s):  
Nakul Nautam Patel ◽  
Lucy Ghali ◽  
Ivan Roitt ◽  
Leonardo Pantoja Munoz ◽  
Richard Bayford
Keyword(s):  
Colorectal Cancer ◽  
Gold Nanoparticles ◽  
Cancer Cells ◽  
Folate Receptor ◽  
Tyrosine Kinase Receptor ◽  
Folate Receptors ◽  
Common Cancer ◽  
Colorectal Cancer Cells ◽  
Different Types

Abstract Colorectal cancer (CRC) is the fourth most common cancer in the world. Due to its asymptomatic nature, CRC is diagnosed at an advanced stage where the survival rate is <5%. Besides, prognosis from CRC treatment using chemotherapy, radiotherapy and surgery often causes undesirable side-effects. As such, gold nanoparticles (GNPs) are envisaged in the field for the diagnosis and treatment of CRC. GNPs have unique physical, chemical and electrical properties at nanoscale which makes them suitable for application in biomedicine. However, for GNPs to become clinically effective, its internalisation efficiency in the cancer cells must be enhanced. Folate receptor-α (FR) are overexpressed in CRC wherein FR helps in uptake of folic acid within the cell. Tyro3, a novel tyrosine kinase receptor, drives cell proliferation and its overexpression is correlated with poor prognosis in CRC. Their upregulated expression in CRC cells relative to normal cells makes them an ideal target for GNPs using active targeting. Therefore, in this study receptors FR and Tyro3 were simultaneously targeted using specific antibody-coated GNPs in order to enhance uptake and internalisation of GNPs in CRC cells in vitro. Four different types of coated-GNPs were synthesised GNPs-PEG, GNPs-anti-FR, GNPs-anti-Tyro3 and GNPs-anti-(FR+Tyro3) and incubated (0ng – 50ng) with three CRC cell lines including CRL1790, CRL2159 and HCT116. Simultaneous targeting of these receptors by GNPs-anti-(FR+Tyro3) was found to be the most effective in internalisation in CRC cells compared with GNPs targeted singly to FR or Tyro3 (p<0.05). Besides this, results show that Tyro3 mediated similar internalisation efficacy as FR (p<0.05) in CRC using ICP-OES.

scholarly journals Combined and selective miR-21 silencing and doxorubicin delivery in cancer cells using tailored DNA nanostructures

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sofia Raniolo ◽  
Valeria Unida ◽  
Giulia Vindigni ◽  
Carmine Stolfi ◽  
Federico Iacovelli ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Chemotherapeutic Agent ◽  
Malignant Tumors ◽  
Folate Receptor ◽  
Dna Nanostructures ◽  
Complementary Sequence ◽  
Cytotoxic Effects ◽  
Folate Receptor Alpha ◽  
Receptor Alpha ◽  
Tumor Associated Antigen

AbstractMicroRNAs play an important role in tumorigenesis and, among them, miR-21 is found to be aberrantly up-regulated in various tumors. The tumor-associated antigen, folate receptor alpha is a GPI-membrane protein overexpressed in many malignant tumors of epithelial origin, including ovarian and cervical cancers. Covalently bound octahedral DNA nanocages were functionalized with folate molecules and utilized as scaffolds to engineer four sequestering units with a miR-21 complementary sequence for obtaining biocompatible Fol-miR21-NC non-toxic nanostructures, to be able to selectively recognize folate receptor alpha-overexpressing cancer cells and sequester the oncogenic miR-21. qPCR assays showed that Fol-miR21-NCs reduce the miR-21 expression up to 80% in cancer cells in the first 2 days of treatment. Functional assays demonstrated that miR-21 sequestering leads to up-regulation of miR-21 tumor suppressor targets (i.e., PTEN and Pdcd4), reduction in cancer cell migration, reduction in proliferation, and increase in cell death. Fol-miR21-NCs can be efficiently loaded with the chemotherapeutic agent doxorubicin. Co-delivery of anti-miR-21 and doxorubicin showed additive cytotoxic effects on tumor cells, paving the way for their use as selective nucleic acid drugs.

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 A pH-sensitive polymer based precise tumor targeting strategy with reduced uptake of nanoparticles by non-cancerous cells

2019 ◽  
Vol 7 (39) ◽  
pp. 5983-5991 ◽  
Author(s):  
Zihou Li ◽  
Xuehua Ma ◽  
Yuanzhi Xia ◽  
Kun Qian ◽  
Ozioma Udochukwu Akakuru ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Tumor Targeting ◽  
Folate Receptor ◽  
Mri Contrast Agent ◽  
Mri Contrast ◽  
Specific Uptake ◽  
Ph Sensitive Polymer ◽  
Cancerous Cells ◽  
Targeting Strategy ◽  
Target Cancer

A T2-weighted MRI contrast agent (SPION-AN-FA@mPEG) can precisely target cancer cells with folate receptor α (FRα) diminishing non-specific uptake by normal healthy cells.

Cytotoxic effects of disulfiram and synergism with cisplatin on ovarian cancer cells in vitro

2018 ◽  
Author(s):  
F Guo ◽  
Z Yang ◽  
J Xu ◽  
J Sehouli ◽  
AE Albers ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Cytotoxic Effects

scholarly journals An Efficient Photodynamic Therapy Treatment for Human Pancreatic Adenocarcinoma

2020 ◽  
Vol 9 (1) ◽  
pp. 192 ◽  
Author(s):  
Alexandre Quilbe ◽  
Olivier Moralès ◽  
Martha Baydoun ◽  
Abhishek Kumar ◽  
Rami Mustapha ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Photodynamic Therapy ◽  
Immune System ◽  
Cancer Cells ◽  
Pancreatic Adenocarcinoma ◽  
Cell Lines ◽  
Folate Receptor ◽  
Mice Model ◽  
Gene And Protein Expression ◽  
The Impact

To date, pancreatic adenocarcinoma (ADKP) is a devastating disease for which the incidence rate is close to the mortality rate. The survival rate has evolved only 2–5% in 45 years, highlighting the failure of current therapies. Otherwise, the use of photodynamic therapy (PDT), based on the use of an adapted photosensitizer (PS) has already proved its worth and has prompted a growing interest in the field of oncology. We have developed a new photosensitizer (PS-FOL/PS2), protected by a recently published patent (WO2019 016397-A1, 24 January 2019). This photosensitizer is associated with an addressing molecule (folic acid) targeting the folate receptor 1 (FOLR1) with a high affinity. Folate binds to FOLR1, in a specific way, expressed in 100% of ADKP or over-expressed in 30% of cases. The first objective of this study is to evaluate the effectiveness of this PS2-PDT in four ADKP cell lines: Capan-1, Capan-2, MiapaCa-2, and Panc-1. For this purpose, we first evaluated the gene and protein expression of FOLR1 on four ADKP cell lines. Subsequently, we evaluated PS2’s efficacy in our cell lines and we assessed the impact of PDT on the secretome of cancer cells and its impact on the immune system. Finally, we evaluate the PDT efficacy on a humanized SCID mouse model of pancreatic cancer. In a very interesting way, we observed a significant increase in the proliferation of activated-human PBMC when cultured with conditioned media of ADKP cancer cells subjected to PDT. Furthermore, to evaluate in vivo the impact of this new PS, we analyzed the tumor growth in a humanized SCID mice model of pancreatic cancer. Four conditions were tested: Untreated, mice (nontreated), mice with PS (PS2), mice subjected to illumination (Light only), and mice subjected to illumination in the presence of PS (PDT). We noticed that the mice subjected to PDT presented a strong decrease in the growth of the tumor over time after illumination. Our investigations have not only suggested that PS2-PDT is an effective therapy in the treatment of PDAC but also that it activates the immune system and could be considered as a real adjuvant for anti-cancer vaccination. Thus, this new study provides new treatment options for patients in a therapeutic impasse and will provide a new arsenal in the fight against PDAC.

Glycoprotein-based bioimaging of HeLa cancer cells by folate receptor and folate decorated graphene quantum dots

2021 ◽  
pp. 106732
Author(s):  
Jafar Soleymani ◽  
Sajjad Azizi ◽  
Soheil Abbaspour ◽  
Mohammad Hasanzadeh ◽  
Mohammad Hossein Somi ◽  
...  
Keyword(s):  
Quantum Dots ◽  
Cancer Cells ◽  
Folate Receptor ◽  
Graphene Quantum Dots
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