Doxorubicin-Loaded Nanoparticles: New Advances in Breast Cancer Therapy

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.

Enhanced antitumor activity of doxorubicin in breast cancer through the use of poly(butylcyanoacrylate) nanoparticles

“…Drug-delivery nanoplatforms have been formulated to protect the antitumor agents that are loaded onto them from in vivo metabolization and elimination (thus optimizing the pharmacokinetic profile of the antitumor agent), and to increase drug accumulation at the site of the tumor, thereby reducing the drug dose needed to obtain a greater antitumor effect and minimizing toxicity. 7 Poly(alkylcyanoacrylates) have been used as promising nanoplatforms in targeted tissue/cell drug delivery, because of their well-known biodegradability and low toxicity in chronic treatments (multiple dosing), good tolerance, and biocompatibility. [8][9][10][11] Furthermore, cell recovery after the metabolization of poly(alkylcyanoacrylate)-based nanoparticles (NPs) occurs easily in vivo, thanks to the very low contact time between healthy tissues and the NP biodegradation products that are carried away from the degradation site by the blood flow.…”

Maghemite Functionalization for Antitumor Drug Vehiculization

“…Nowadays there has been an enormous amount of research on the doxorubicin union with nanoparticulate carriers (Nawara et al, 2012;Du et al, 2011;Nowicka et al, 2009). This combination has resulted in controlled drug release over increased period of time, with the subsequent raise in efficiency and decrease in side effects (Jia et al, 2012;Prados et al, 2012). DOX has been found to be more efficient if attached to hydrophilic nanoparticles which are able to enter into the cell more profoundly than the cytotoxic agent alone, and therefore they can increase uptake of free anthracycline drug (Guo et al, 2008;Patil et al, 2008;Wang, 2007).…”

FGFR4 Links Glucose Metabolism and Chemotherapy Resistance in Breast Cancer

“…Doxorubicin (ADR), a derivative of the natural product daunomycin, works by intercalating DNA and inhibiting the religation step of topoisomerase II. It has long been used as a first-line chemotherapeutic drug to treat breast cancer [3-5]. Unfortunately, doxorubicin drug resistance appears in nearly 50% of treated patients [3].…”

“…It has long been used as a first-line chemotherapeutic drug to treat breast cancer [3-5]. Unfortunately, doxorubicin drug resistance appears in nearly 50% of treated patients [3]. The development of chemoresistance in breast cancer can be either intrinsic or acquired.…”