ABSTRACT
BACKGROUND: Discovering new chemotherapy drugs and techniques with the least side effects is one of the most important and challenging issues in recent years worldwide. Chlorambucil is an anticancer drug that is still commonly used as a primary treatment in treating some cancers, but it can cause side effects. OBJECTIVE: In this study, we decided to use chitosan as a carrier to enhance the uptake of chlorambucil and reduce the toxicity of this drug. METHODS: After producing this nanoconjugate compound and analysing its structure by FTIR, DLS and AFM analysis, we investigated the therapeutic and biological effects of this nanoconjugate compound on the MCF-7 cell line (breast cancer). RESULTS: The results of the MTT assay showed that this nanoconjugate compound not only retained its anticancer effect against chlorambucil but also showed less abnormal toxicity. In addition, in vitro cellular uptake by flow cytometry indicated the better uptake final product into the MCF-7 cells. The detection of apoptosis induced cell death was confirmed by RT-PCR. CONCLUSION: This study has created a prospective pathway for targeting cancer cells using chitosan.
Subject(s)
Antineoplastic Agents , Breast Neoplasms , Chitosan , Chlorambucil , Nanoconjugates , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/pharmacology , Breast Neoplasms/drug therapy , Cell Proliferation/drug effects , Chlorambucil/administration & dosage , Chlorambucil/pharmacology , Humans , MCF-7 Cells , Prospective StudiesABSTRACT
Gadolinium as a contrast agent in MRI technique combined with DTPA causes contrast induced nephropathy (CIN) and nephrogenic systemic fibrosis (NSF) which can reduce by usage of antioxidants such as N-acetyl cysteine by increasing the membrane's permeability leads to lower cytotoxicity. In this study, N-acetyl cysteine-PLGA Nano-conjugate was synthesized according to stoichiometric rules of molar ratios andafter assessment by FTIR, NMR spectroscopy and Atomic Force Microscopy (AFM) imaging was combined with Magnevist® (gadopentetate dimeglumine) and its effects on the renal cells were evaluated. MTT [3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide] and cellular uptake assays have indicated relatively significant toxicity of magnevist (P < 0.05) on three cell lines including HEK293, MCF7 and L929 compared to other synthesized ligands that shown no toxicity. Moreover, systemic evaluation has shown no notable changes of blood urea nitrogen (BUN) and creatinine in kidney of mice. In consequence, antioxidant effect was increased as well as the renal toxicity of the contrast agent reduced at the cell level. As a result, PLGA-NAC nano-conjugate can be a promising choice for decreasing the magnevist toxicity for treatment and prevention of CIN and will be able to open a new horizon to research on reduction of toxicity of contrast agents by using nanoparticles.
Subject(s)
Acetylcysteine , Gadolinium DTPA , Nanoconjugates , Polylactic Acid-Polyglycolic Acid Copolymer , Acetylcysteine/chemistry , Acetylcysteine/toxicity , Animals , Cell Survival/drug effects , Cells, Cultured , Contrast Media/chemistry , Contrast Media/pharmacokinetics , Drug Delivery Systems , Gadolinium DTPA/chemistry , Gadolinium DTPA/pharmacokinetics , HEK293 Cells , Humans , Kidney/cytology , Kidney/metabolism , MCF-7 Cells , Mice , Nanoconjugates/chemistry , Nanoconjugates/toxicity , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Polylactic Acid-Polyglycolic Acid Copolymer/toxicityABSTRACT
Breast cancer is the most common type of cancer in women worldwide. There have been many efforts for early breast cancer detection and among them molecular imaging have been extremely of high importance. Single-photon emission computed tomography (SPECT/CT) is a kind of imaging technique able to reveal crucial information with using radiopharmaceuticals. In this study, Technetium-99m-(DOTA-NHS-ester)-Methionine radiopharmaceutical was synthesized. Between 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid mono-N-hydroxysuccinimide ester (DOTA-HNS ester) (MACROCYCLICS, DOTA-NHS ester, Plano, Texas, USA) and methionine(marker) were conjugated. The DOTA-HNS ester-Methionine was labeled with Technetium-99m (Inter-Medical, Technetium-99m, Bergamo, Italy). The synthesized radiopharmaceutical was used in SPECT/CT imaging for breast cancer diagnosis. For radiopharmaceutical evaluation, MTT assay for cellular toxicity, biodistribution, cellular uptake and radiochemical purity were employed.Technetium-99m-(DOTA-NHS-ester)-Methionine radiochemical had less cellular toxicity in human embryonic kidney cells 293 cell line (HEK293). Cellular uptake was indicated higher percent with use of Methionine as a marker, and radiochemical purity was high. Based on the results Technetium-99m-(DOTA-NHS-ester)-Methionine radiochem may be a better option for early detection of breast cancer. Further study is recommended to confirm these findings in clinical practice.
