Search

Metastatic cancer is responsible for 90% of deaths in world. Usage of nano-carriers improve the delivery and efficacy of chemotherapeutic agents. Recent studies suggest that decoration of the surface of nano-carriers with various targeting agents may further improve their overall therapeutic efficacy. Using specified peptides in targeted drug delivery is a key point in recent researches. In this study, tumor metastasis targeting (TMT) homing peptide was applied as a targeting group to improve specific drug delivery to tumor cells. TMT peptide is conjugated to poly ethylene glycol-poly caprolactone (PEG-PCL) micellar nanoparticles as carriers for targeted delivery of cabazitaxel to metastatic breast cancer cells. Synthesis of PEG-PCL copolymer was performed by amidation reaction between carboxylic acid group of PEG and amine group of PCL. Nanomicelles were prepared via solvent evaporation method. TMT peptide was covalently conjugated onto nanomicelles through the amine group of PEG. TMT-PEG-PCL nanoparticles were analyzed by Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), dynamic light scattering (DLS), gel permeation chromatography (GPC) and nuclear magnetic resonance (NMR). Toxicity and cellular uptake of nanomicelles were investigated by in vitro cytotoxicity assays and confocal scanning microscopy in MCF-7 (non-metastatic breast cancer cells) and MDA-MB-231 (metastatic breast cancer cells). The final nanomicelles had about 110nm mean size and encapsulation efficiency of 82.5%. Treatment of metastatic breast cancer cells with targeted nanomicelles significantly increased the necrosis rate to 65%, compared to 33% in non-targeted nanomicelles and 8% in control group. The MDA-MB-231 cells treated with targeted nanomicelles exhibited a strong increase in the fluorescence intensity of coumarin in comparison to the cells treated with non-targeted nanomicelles (p<0.001). It could be concluded that the present carrier has the potential to be considered in treatment of metastatic breast cancer cells., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Chitosan-coated human serum albumin nanoparticles were functionalized by MUC1 aptamer to obtain a selective drug carrier toward cancers overexpressing MUC1. The negative charges of albumin nanoparticles were shifted to positive charges by surface modification with chitosan, and MUC1 was conjugated through an acrylate spacer. The cytotoxicity of targeted nanoparticles was significantly more than non-aptamer nanoparticles, and also the chitosan-coated nanoparticles had more cytotoxic effects than the negatively charged albumin nanoparticles. The IC 50 of targeted nanoparticles was 28 and 26% of free paclitaxel in MCF7 and T47D cells at 48h, respectively. Confocal laser scanning electron microscopy showed that aptamer conjugation and positive charge increase the cellular uptake. 66% of paclitaxel was released within 32h, but 100% of drug was released at pH=5.5 (similar cancer cells). The paclitaxel plasma amount was at a good level of 17.6% at 2h for increasing the chance of cellular uptake., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: A folate-receptor-targeted poly (lactide-co-Glycolide) (PLGA)-Polyethylene glycol (PEG) nanoparticle is developed for encapsulation and delivery of disulfiram into breast cancer cells. After a comprehensive characterization of nanoparticles, cell cytotoxicity, apoptosis induction, cellular uptake and intracellular level of reactive oxygen species are analyzed. In vivo acute and chronic toxicity of nanoparticles and their efficacy on inhibition of breast cancer tumor growth is studied., Results: The folate-receptor-targeted nanoparticles are internalized into the cells, induce reactive oxygen species formation, induce apoptosis and inhibit cell proliferation more efficiently compared to the untargeted nanoparticles. The acute and toxicity test show the maximum dose of disulfiram equivalent of nanoparticles for intra-venous injection is 6 mg/kg while show significant decrease in the breast cancer tumor growth rate., Conclusion: It is believed that the developed formulation could be used as a potential vehicle for successful delivery of disulfiram, an old and inexpensive drug, into breast cancer cells and other solid tumors.

Today, using nanoparticle-based drug delivery systems has expanded to avoid anticancer side effects. Taxanes are important chemotherapeutic agents in the treatment of metastatic breast cancer. In this study, docetaxel (DTX)-loaded human serum albumin (HSA) nanoparticles (NPs) were prepared and characterized. Drug toxicity of the nanoparticles was measured by MTT assay with different drug concentrations (0.01, 0.1, 0.5, 1 and 5 μM) at different incubation times (24, 48 and 72 h). Expression of BAX/BCL2 mRNA levels was determined by real-time PCR. The size of NPs prepared and used in our study was about 147 nm with surface charge of -29.6 mV. Results obtained from MTT assay showed that 0.5 μM of free drug had 50 % toxicity on MCF-7 cells after 48-h incubation. Real-time PCR results showed an increase in expression of BAX and no change for BCL2. In conclusion, a significant overexpression of BAX gene and changes in BAX/BCL2 ratio were observed for DTX-loaded HSA nanoparticles compared with free DTX and may provide a potential therapy to inhibit anticancer drug resistance.