摘要
Aim:Resistance to chemotherapy is a major limiting factor that hamper the effectiveness of anticancer therapies.Doxorubicin is an antineoplastic agent used in the treatment of a wide range of cancers.However,it presents several limitations such as dose-dependent cardiotoxicity,lack of selectivity for tumor cells,and induced cell resistance.Nanotechnology represents a promising strategy to avoid these drawbacks.In this work,new albumin-based nanoparticles were formulated for the intracellular delivery of doxorubicin with the aim to overcome cancer drug resistance.Methods:Glycol chitosan-coated and uncoated albumin nanoparticles were prepared with a tuned coacervation method.The nanoformulations were in vitro characterized evaluating the physicochemical parameters,morphology,and in vitro release kinetics.Biological assays were performed on A2780res and EMT6 cells from human ovarian carcinoma and mouse mammary cell lines resistant for doxorubicin,respectively.Results:Cell viability assays showed that nanoparticles have higher cytotoxicity than the free drug.Moreover,at low concentrations,both doxorubicin-loaded nanoparticles inhibited the cell colony formation in a greater extent than drug solution.In addition,the cell uptake of the different formulations was investigated by confocal microscopy and by the HPLC determination of doxorubicin intracellular accumulation.The nanoparticles were rapidly internalized in greater extent compared to the free drug.Conclusion:Based on these results,doxorubicin-loaded albumin nanoparticles might represent a novel platform to overcome the mechanism of drug resistance in cancer cell lines and improve the drug efficacy.
基金
supported by funds from University of Turin(ex60%)
from Associazione Italiana per la Ricerca sul Cancro(AIRC,IG-#19957)
AIRC 5 per Mille,Special Program on Metastatic Disease(#21052).
