Drug delivery approaches for breast cancer

Abstract

Breast cancer is one of the most common cancers affecting women worldwide. The controlled release of drugs to the precise site of the disease using a nanocarrier vehicle increases the therapeutic efficiency of the drugs. Nanotechnology-based approaches used to endorse clinical improvement from a disease also help to understand the interaction of malignant cells with their microenvironment. Receptor-based targeting is another approach for drug delivery which is undergoing clinical trials. Nanoparticles (NPs) delivery has been proven to promise high loading capacity, less toxicity, and stability of the drugs or biomolecules compared to traditional chemotherapeutic drugs. The goal of this review is to present the current problems of breast cancer therapy and discuss the NP-based targeting to overcome the hurdles of conventional drug therapy approach.

Keywords: breast cancer; drug delivery systems; nanoparticles.

Figure 1

Drug delivery systems for breast cancer. Abbreviations: SPIO, superparamagnetic iron oxide; HER-2, human epidermal growth factor receptor 2; EGFR, epidermal growth factor receptor; IGF-IR, insulin-like growth factor I receptor; VEGFR, vascular endothelial growth factor receptor.

Figure 2

Schematic representation of nanoparticle-based drug delivery mechanism in drug-resistant breast cancer cells. The most common mechanism of drug efflux in cancer cells is mediated by ABC transporters P-glycoprotein, BCRP, and ABCG2. Multidrug resistance protein consisting of nuclear-binding domain and transmembrane domain binds to the receptors on the surface of target tumor cells and functions in efflux of chemotherapeutic drugs such as taxol and anthracycline. However, delivery approaches using targeted drug nanocarriers (dendrimers, liposomes, micelles, polysomes) overcome the chemoresistance in tumor cells by activation of proapoptotic mediators, resulting in cell death. Abbreviation: ABC, ATP-binding cassette.

Figure 3

Receptor-mediated drug delivery to metastatic breast cancer cells. Nanocarrier-based drug targeting using receptor-mediated pathways governs the major therapeutic approach for the active sites in tumor cells. Ligand–nanoparticle conjugate binds to the receptors (EGFR, VEGFR, HER-2, IGF-IR) on the membrane, mediates internalization of nanoparticles through endocytosis, and releases the drugs by lysosomal degradation to the active sites of tumor cells. Abbreviations: EGFR, epidermal growth factor receptor; VEGFR, vascular endothelial growth factor receptor; HER-2, human epidermal growth factor receptor 2; IGF-IR, insulin-like growth factor I receptor; NPs, nanoparticles.