Synthesis and Evaluation of 198Au/PAMAM-MPEG-FA against Cancer Cells

2020 ◽  
Vol 20 (10) ◽  
pp. 1250-1265
Author(s):  
Reza Rezaei ◽  
Simin Janitabar Darzi ◽  
Mahnaz Yazdani

Background: There is a significant dearth of clinical biochemistry researches to evaluate the facility of exploitation of folate targeted radioactive gold-labeled anti-cancer drugs against various cancer cell lines. Objective: The aim of this paper was to develop a gold-based compound with an efficient therapeutic potential against breast cancer. To this end, the synthesis of the 198Au/PAMAM-MPEG-FA composite was considered here. Methods: The radioactive gold (198Au) nanoparticles were encapsulated into Folic acid (FA)-targeted Polyamidoamine dendrimer (PAMAM) modified with Maleimide-Polyethylene glycol Succinimidyl Carboxymethyl ester (MPEG). After that, anticancer assessments of the prepared 198Au/PAMAM-MPEG-FA hybrid mater against breast cancer were investigated. : Further studies were also devised to compare the anticancer capabilities of the 198Au/PAMAM-MPEG-FA composite with the synthesized P-MPEG, 197Au/P-MPEG, 197Au/P-MPEG-FA, 197Au/P-FA and 198Au/P-MPEG-FA conjugates. The prepared drugs were characterized by means of various analytical techniques. The radionuclidic purity of the 198Au/P-MPEG-FA solution was determined using High Purity Germanium (HPGe) spectroscopy and its stability in the presence of human serum was studied. The cell uptake and toxicity of the prepared drugs were evaluated in vitro, and some comparative studies of the toxicity of the drugs were conducted towards the MCF7 (Human breast cancer cell), 4T1 (Mice breast adenocarcinoma cell) and C2C12 (Mice muscle normal cell). Results: The results showed that cell uptake of 198Au/P-MPEG-FA nanoparticles is high in the 4T1 cell line and the order of uptake is as 4T1> MCF7> C2C12. Moreover, of the tested compounds, 198Au/P-MPEG-FA had the highest toxicity towards the cancerous 4T1 and MCF7 in all concentrations after 24, 48 and 72h (P < 0.001). Furthermore, the cytotoxicity of the drugs was concentration-dependent. Conclusion: On the basis of the present research, 198Au/P-MPEG-FA has been proposed as a good candidate for the induction of cell death in breast cancer, although further experimental and clinical investigations are required.

2018 ◽  
Vol 16 (2) ◽  
pp. 127-137
Author(s):  
Paula Sofia Coutinho Medeiros ◽  
Ana Lúcia Marques Batista de Carvalho ◽  
Cristina Ruano ◽  
Juan Carlos Otero ◽  
Maria Paula Matos Marques

Background: The impact of the ubiquitous dietary phenolic compound p-coumaric acid on human breast cancer cells was assessed, through a multidisciplinary approach: Combined biological assays for cytotoxicity evaluation and biochemical profiling by Raman microspectroscopic analysis in cells. </P><P> Methods: Para-coumaric acid was shown to exert in vitro chemoprotective and antitumor activities, depending on the concentration and cell line probed: a significant anti-invasive ability was detected for the triple-negative MDA-MB-231 cells, while a high pro-oxidant effect was found for the estrogen- dependent MCF-7 cells. A striking cell selectivity was obtained, with a more noticeable outcome on the triple-negative MDA-MB-231 cell line. Results: The main impact on the cellular biochemical profile was verified to be on proteins and lipids, thus justifying the compound´s anti-invasive effect and chemoprotective ability. Conclusion: p-Coumaric acid was thus shown to be a promising chemoprotective/chemotherapeutic agent, particularly against the low prognosis triple-negative human breast adenocarcinoma.


2020 ◽  
Vol 15 (2) ◽  
pp. 165-173
Author(s):  
Elaheh Amini ◽  
Mohammad Nabiuni ◽  
Seyed Bahram Behzad ◽  
Danial Seyfi ◽  
Farhad Eisvand ◽  
...  

Background: Breast carcinoma is a malignant disease that represents the most common non-skin malignancy and a chief reason of cancer death in women. Large interest is growing in the use of natural products for cancer treatment, especially with goal of suppression angiogenesis, tumor cell growth, motility, as well as invasion and metastasis with low/no toxicity. It is evident from recent patents on the anticancer properties of sesquiterpene lactones such as parthenolide. Objective: In this study, using MDA-MB-231 cells of a human breast adenocarcinoma, the effects of aguerin B, as a natural sesquiterpene lactone, has been evaluated, in terms of the expression of metastatic-related genes (Pak-1, Rac-1 and HIF-1α). Methods: Cytotoxicity of aguerin B was tested toward MDA-MB-231 breast tumor cells using MTT. Scratch assay was accomplished to evaluate the tumor cell invasion. To understand the underlying molecular basis, the mRNA expressions were evaluated by real time PCR. Results: It was found that aguerin B significantly inhibited human breast cancer cell growth in vitro (IC50 = 2μg/mL) and this effect was accompanied with a persuasive suppression on metastasis. Our results showed that aguerin B in IC50 concentration down-regulated Rac-1, Pak-1, Hif-1α and Zeb-1 transcriptional levels. Conclusion: Taken together, this study demonstrated that aguerin B possessed potential anti-metastatic effect, suggesting that it may consider as a potential multi target bio compound for treatment of breast metastatic carcinoma.


2014 ◽  
Vol 210 ◽  
pp. 51-63 ◽  
Author(s):  
Kumaravel Mohankumar ◽  
Sankar Pajaniradje ◽  
Subhashree Sridharan ◽  
Vivek Kumar Singh ◽  
Larance Ronsard ◽  
...  

2020 ◽  
Vol 15 (2) ◽  
pp. 143-151
Author(s):  
Sumit Bera ◽  
Subhasis Maity ◽  
Balaram Ghosh ◽  
Animesh Ghosh ◽  
Tapan K. Giri

Background: Capsaicin is a pungent component of chili peppers that suppresses the growth of various cancer cell lines including breast cancer. However, it shows extremely low oral bioavailability due to its poor water solubility. Objective: The objective of the present work was to improve the solubility and dissolution rate of capsaicin. Methods: Solid dispersions were prepared by the solvent evaporation method using different molar ratios of capsaicin and urea (1:1, 1:2, and 1:3). Differential Scanning Calorimetry (DSC) and X-Ray Diffraction (XRD) study were used to characterize the solid dispersion. Solid dispersions were evaluated for solubility, dissolution rate and in vitro cytotoxicity in breast cancer cell lines. Results: XRD and DSC studies exhibited the reduced crystallinity of a drug in solid dispersion. Phase solubility study shows that the drug solubility increased by increasing carrier concentration. In vitro release study of the solid dispersion showed the faster dissolution of a drug with increasing carrier concentration. Solid dispersion formulation effectively inhibited the growth of MCF-7 human breast cancer and MDA-MB-231 triple negative human breast cancer cells in an MTT assay that measures metabolic activity, but only slightly decreased cell viability when compared to capsaicin alone. Conclusion: The present study demonstrated that solid dispersion of capsaicin in PEG 6000 overcomes the problems related to the poor aqueous solubility of this drug and improving its dissolution rate.


NANO ◽  
2014 ◽  
Vol 09 (07) ◽  
pp. 1450073 ◽  
Author(s):  
XING REN ◽  
HAILONG HUANG ◽  
JINGYUAN WANG ◽  
GUANG SUN ◽  
ZHELI XU

This research is aimed to develop a novel kind of biomarker based on water-soluble quantum dots (QDs) conjugated with estrogen receptor (ER) for the detection of breast cancer (BC). To achieve the purpose, hydrophobic octadecylamine-coated QDs were encapsulated with amphiphilic biocompatible centipede-like polymer p(aspartate)- Na -graft-p(ethylene glycol)-dodecylamine (PASP- Na -g-PEG-DDA), and then modified with ER monoclonal antibodies, which is one of the most popular biomarkers for the detection and management of breast cancer worldwide. The targeted QDs kept the original optical property of QDs. The cytotoxicity in vitro experiments showed that QDs-ER probes had no obvious toxic side effects. Remarkably, confocal laser scanning microscopy (CLSM) revealed that the localized fluorescence appeared around the nucleus of human breast cancer cell MCF7 (ER positive) compared with that of human breast cancer cell MBA-MD-231 (ER negative). According to the above analysis, this new kind of probe has great potential in the diagnosis of breast tumor in vitro in future clinical application.


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