Doxorubicin-Loaded Nanoparticles: New Advances in Breast Cancer Therapy

Jose      Prados; Consolacion      Melguizo; Raul      Ortiz; Celia      Velez; Pablo      J. Alvarez; Jose      L. Arias; Maria      A. Ruiz; Visitacion      Gallardo; Antonia      Aranega

doi:10.2174/187152012803529646

Abstract

Doxorubicin, one of the most effective anticancer drugs currently known, is commonly used against breast cancer. However, its clinical use is restricted by dose-dependent toxicity (myelosuppression and cardiotoxicity), the emergence of multidrug resistance and its low specificity against cancer cells. Nanotechnology is a promising alternative to overcome these limitations in cancer therapy as it has been shown to reduce the systemic side-effects and increase the therapeutic effectiveness of drugs. Indeed, the numerous nanoparticle-based therapeutic systems developed in recent years have shown low toxicity, sustained drug release, molecular targeting, and additional therapeutic and imaging functions. Furthermore, the wide range of nanoparticle systems available may provide a solution to the different problems encountered during doxorubicin-based breast cancer treatment. Thus, a suitable nanoparticle system may transport active drugs to cancer cells using the pathophysiology of tumours, especially their enhanced permeability and retention effects, and the tumour microenvironment. In addition, active targeting strategies may allow doxorubicin to reach cancer cells using ligands or antibodies against selected tumour targets. Similarly, doxorubicin resistance may be overcome, or at least reduced, using nanoparticles that are not recognized by P-glycoprotein, one of the main mediators of multidrug resistance, thereby resulting in an increased intracellular concentration of drugs. This paper provides an overview of doxorubicin nanoplatform-based delivery systems and the principal advances obtained in breast cancer chemotherapy.

Keywords: Breast cancer, Chitosan, Cytotoxic drugs, Doxorubicin, Nanoparticles, Drug resistance, P-glycoprotein, Doxorubicin, hydrophilic, hydrophobic