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
Designing a unique theranostic biocompatible, biodegradable, and cost-effective agent which is easy to be synthesized as a biohybrid material was the aim of this study. In this matter, asparagine attached to anionic linear globular dendrimer G2 (as a biocompatible, biodegradable, and cost-effective agent which is negatively charged nanosized and water soluble polymer that outweighs other traditionally used dendrimers) and finally contrast agent (Gd3+) was loaded (which made complexes) in synthesized asparagine-dendrimer. Observations revealed that, in addition to successful colon cancer and brain targeting, Gd3+-dendrimer-asparagine, the proposed theranostic agent, could increase T1 MR relaxation times, decrease T2 MR relaxation times significantly, and improve contrast of image as well as illustrating good cellular uptake based on florescent microscopy/flow cytometry and ICP-mass data. In addition to that, it increased tumor growth inhibition percentage (TGI%) significantly compared to FDA approved contrast agent, Magnevist. Totally, Gd3+-anionic linear globular dendrimer G2-asparagine could be introduced to the cancer imaging/therapy (theranostics) protocols after in vivo MR and fluorescent analysis and passing clinical trials. Hence, this nanotheranostic agent would be a promising candidate for brain drug delivery and imaging in the future.
