scholarly journals CYTOTOXIC EVALUATION OF ANTICANCER FOLATE DECORATED CARBOPLATIN LOADED ALBUMIN NANOPARTICLES USING FOLATE RECEPTOR OVEREXPRESSING CELL LINES

2021 ◽  
Vol 64 (2) ◽  
pp. 109-121
Author(s):  
Hosam Abdelwahab
Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 953
Author(s):  
Chuan Xu ◽  
Annie Wang ◽  
Ke Geng ◽  
William Honnen ◽  
Xuening Wang ◽  
...  

Severe acute respiratory syndrome-related coronavirus (SARS-CoV-2), the causative agent of coronavirus disease 19 (COVID-19), enters cells through attachment to the human angiotensin converting enzyme 2 (hACE2) via the receptor-binding domain (RBD) in the surface/spike (S) protein. Several pseudotyped viruses expressing SARS-CoV-2 S proteins are available, but many of these can only infect hACE2-overexpressing cell lines. Here, we report the use of a simple, two-plasmid, pseudotyped virus system comprising a SARS-CoV-2 spike-expressing plasmid and an HIV vector with or without vpr to investigate the SARS-CoV-2 entry event in various cell lines. When an HIV vector without vpr was used, pseudotyped SARS-CoV-2 viruses produced in the presence of fetal bovine serum (FBS) were able to infect only engineered hACE2-overexpressing cell lines, whereas viruses produced under serum-free conditions were able to infect a broader range of cells, including cells without hACE2 overexpression. When an HIV vector containing vpr was used, pseudotyped viruses were able to infect a broad spectrum of cell types regardless of whether viruses were produced in the presence or absence of FBS. Infection sensitivities of various cell types did not correlate with mRNA abundance of hACE2, TMPRSS2, or TMPRSS4. Pseudotyped SARS-CoV-2 viruses and replication-competent SARS-CoV-2 virus were equally sensitive to neutralization by an anti-spike RBD antibody in cells with high abundance of hACE2. However, the anti-spike RBD antibody did not block pseudotyped viral entry into cell lines with low abundance of hACE2. We further found that CD147 was involved in viral entry in A549 cells with low abundance of hACE2. Thus, our assay is useful for drug and antibody screening as well as for investigating cellular receptors, including hACE2, CD147, and tyrosine-protein kinase receptor UFO (AXL), for the SARS-CoV-2 entry event in various cell lines.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
S. Mohana ◽  
M. Ganesan ◽  
N. Rajendra Prasad ◽  
D. Ananthakrishnan ◽  
D. Velmurugan

An amendment to this paper has been published and can be accessed via the original article.


2020 ◽  
Vol 9 (1) ◽  
pp. 192 ◽  
Author(s):  
Alexandre Quilbe ◽  
Olivier Moralès ◽  
Martha Baydoun ◽  
Abhishek Kumar ◽  
Rami Mustapha ◽  
...  

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.


Author(s):  
Giuseppe Toffoli ◽  
Giuseppe Corona ◽  
Barbara Tolusso ◽  
Franca Sartor ◽  
Roberto Sorio ◽  
...  

2002 ◽  
Vol 11 (8) ◽  
pp. 803-811 ◽  
Author(s):  
Luca Polastri ◽  
Francesca Galbiati ◽  
Franco Folli ◽  
Alberto M. Davalli

We recently developed two rat pituitary GH3 cell clones engineered to secrete human insulin (InsGH3). InsGH3 cells convert proinsulin into mature insulin, which is partially stored into a readily releasable pool of secretory granules. The efficiency of these processes, however, is relatively low in these cells, either in vitro or in vivo. This study was aimed at determining whether carboxypeptidase E (Cpe) overexpression can increase proinsulin processing and regulated secretion by InsGH3 clones. Indeed, in its membrane-bound form Cpe works as sorting receptor for the regulated secretory pathway of many hormones while, in its soluble form, Cpe takes part to the late step of insulin maturation. We obtained two Cpe-overexpressing cell lines from two different InsGH3 clones (InsGH3/C1 and C7). In the Cpe-overexpressing cell lines, derived from InsGH3 of clone 1 (InsGH3/C1-HACpe), in which the membrane-bound form of exogenous Cpe is accounted for by 90% of total Cpe immunoreactivity, we observed an increase in proinsulin gene expression, and in basal and stimulated insulin secretion compared with the original clone. In contrast, in the Cpe-overexpressing cell line derived from InsGH3 of clone 7 (InsGH3/C7-HACpe), where the exogenous membrane-bound form was only 60% of total Cpe, we detected a decrease in basal insulin release and a modest, albeit significant, increase in intracellular proinsulin processing. In conclusion, Cpe overexpression can increase regulated insulin secretion and proinsulin processing in InsGH3 cells; however, such improvements appear quantitatively and qualitatively modest.


Biomedicines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 76 ◽  
Author(s):  
Fiona Maiyo ◽  
Moganavelli Singh

The development of a biocompatible and nontoxic gene delivery vehicle remains a challenging task. Selenium nanoparticles (SeNPs) have the potential to increase delivery efficiency, to reduce side effects, and to improve therapeutic outcomes. In this study, chitosan (Ch) functionalized folate (FA)-targeted SeNPs were synthesized, characterized, and evaluated for their potential to bind, protect, and safely deliver Fluc-siRNA in vitro. SeNPs of less than 100 nm were successfully synthesised and further confirmed using UV-vis and Fourier transform infrared spectroscopy, transmission electron microscopy, and nanoparticle tracking analysis. Cell viability studies were conducted in vitro in selected cancer and non-cancer cell lines. Folate receptor (FOLR1) targeted and nontargeted luciferase gene silencing studies were assessed in the transformed Hela-tat-Luc cell line expressing the luciferase gene. Targeted and nontargeted SeNP nanocomplexes showed minimal toxicity in all cell lines at selected w/w ratios. Maximum gene silencing was achieved at optimum w/w ratios for both nanocomplexes, with Selenium-chitosan-folic acid (SeChFA) nanocomplexes showing slightly better transgene silencing, as supported by results from docking studies showing that SeChFA nanocomplexes interacted strongly with the folate receptor (FOLR1) with high binding energy of −4.4 kcal mol−1.


BMC Cancer ◽  
2018 ◽  
Vol 18 (1) ◽  
Author(s):  
S. Mohana ◽  
M. Ganesan ◽  
N. Rajendra Prasad ◽  
D. Ananthakrishnan ◽  
D. Velmurugan

Leukemia ◽  
2009 ◽  
Vol 23 (2) ◽  
pp. 431-431
Author(s):  
Z Diaz ◽  
K K Mann ◽  
S Marcoux ◽  
M Kourelis ◽  
M Colombo ◽  
...  

2003 ◽  
Vol 77 (24) ◽  
pp. 13433-13438 ◽  
Author(s):  
Graham Simmons ◽  
Andrew J. Rennekamp ◽  
Ning Chai ◽  
Luk H. Vandenberghe ◽  
James L. Riley ◽  
...  

ABSTRACT Folate receptor alpha (FRα) has been described as a factor involved in mediating Ebola virus entry into cells (6). Furthermore, it was suggested that interaction with FRα results in internalization and subsequent viral ingress into the cytoplasm via caveolae (9). Descriptions of cellular receptors for Ebola virus and its entry mechanisms are of fundamental importance, particularly with the advent of vectors bearing Ebola virus glycoprotein (GP) being utilized for gene transfer into cell types such as airway epithelial cells. Thus, the ability of FRα to mediate efficient entry of viral pseudotypes carrying GP was investigated. We identified cell lines and primary cell types such as macrophages that were readily infected by GP pseudotypes despite lacking detectable surface FRα, indicating that this receptor is not essential for Ebola virus infection. Furthermore, we find that T-cell lines stably expressing FRα are not infectible, suggesting that FRα is also not sufficient to mediate entry. T-cell lines lack caveolae, the predominant route of FRα-mediated folate metabolism. However, the coexpression of FRα with caveolin-1, the major structural protein of caveolae, was not able to rescue infectivity in a T-cell line. In addition, other cell types lacking caveolae are fully infectible by GP pseudotypes. Finally, a panel of ligands to and soluble analogues of FRα were unable to inhibit infection on a range of cell lines, questioning the role of FRα as an important factor for Ebola virus entry.


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