Chemotherapeutic agents have been used extensively in breast cancer remedy. However, most anticancer drugs cannot differentiate between cancer cells and normal cells, leading to toxic side effects. Also, the resulted drug resistance during chemotherapy reduces treatment efficacy. The development of targeted drug delivery offers great promise in breast cancer treatment both in clinical applications and in pharmaceutical research. Conjugation of nanocarriers with targeting ligands is an effective therapeutic strategy to treat cancer diseases. In this review, we focus on active targeting methods for breast cancer cells through the use of chemical ligands such as antibodies, peptides, aptamers, vitamins, hormones, and carbohydrates. Also, this review covers all information related to these targeting ligands, such as their subtypes, advantages, disadvantages, chemical modification methods with nanoparticles and recent published studies (from 2015 to present). We have discussed 28 different targeting methods utilized for targeted drug delivery to breast cancer cells with different nanocarriers delivering anticancer drugs to the tumors. These different targeting methods give researchers in the field of drug delivery all the information and techniques they need to develop modern drug delivery systems.

Epirubicin (Epr) is an effective chemotherapeutic drug; however, the clinical amenability of Epr is limited by its highly toxic interaction with normal cells. This toxicity can be decreased by utilizing nanocarriers and targeted drug delivery systems. This work describes an approach for the delivery of Epr via encapsulation in the horse spleen apoferritin (HsAFr) cavity. The encapsulation was achieved by the disassembling of apoferritin into subunits at pH 2 followed by its reformation at pH 7.4 in the presence of Epr. The surface of HsAFr-encapsulated Epr was modified with folic acid (FA) for optimal targeting of breast cancer cells (MCF-7). The use of FA to functionalize HsAFr could enhance the cellular uptake efficiency via FA-receptor-mediated endocytosis. UV-vis spectroscopy, fluorescence spectroscopy, circular dichroism (CD) and transmission electron microscopy (TEM) were utilized for structural characterization of the HsAFr-Epr and HsAFr-Epr-FA complexes. The comparison of the anti-cancer activities across the HsAFr-Epr-FA complex and the free Epr drug was performed using the MTT viability assay on MCF-7.

Background: Thiazolidine-4-one is a promising class of heterocyclic compounds with interesting pharmacological and biological activities, such as anticancer and antibacterial. Therefore, many researchers have synthesized thiazolidine-4-ones and evaluated their biological potential for developing new drugs. Objective: In this study, two novel thiazolidine-4-one derivatives (T1 and T2) were synthesized and evaluated for their antibacterial activity toward Staphylococcus aureus, Escherichia coli and Proteus mirabilis. Also, the cytotoxic activities of compounds T1 and T2 were estimated against MCF-7 (HER2+, ER+ and ER+) and MDA-MB-231 (triple-negative) human breast cancer cell lines. The chemical structure of compounds T1 and T2 was proven using spectral techniques (FT-IR, 1HNMR, and 13C-NMR) and CHN elemental analysis. Methods: The synthesis of thiazolidine-4-one compounds was performed in two steps. The first step consisted of the formation of Schiff bases S1 and S2. In the second step, the synthesized Schiff bases were reacted with thioglycolic acid to prepared thiazolidine-4-one compounds T1 and T2. Hemolysis assay, molecular docking, cytotoxicity activity (MTT assay) and antibacterial activity (disc diffusion assay) were studied. Results: The hemolysis study demonstrated that the hemolytic ratio of compounds T1 and T2 at (1, 2 and 3) mg/ml was less than 4%. MTT assay showed that 100 µg/ml of compounds T1 and T2 diminish the MCF-7 cell growth up to 80.05 ± 1.72 and 69.85 ± 3.26 respectively after 72 hrs, while the same concentration of compounds T1 and T2 reduces the MDA-MB-231 cell growth up 70.28 ± 2.31 and 57.15 ± 1.49, respectively. The inhibition zone of compounds T1 and T2 were 12 mm at 50 mg/ml and 10 mm at 5 mg/ml in E. coli bacteria. Furthermore, a docking study was carried out to investigate the affinity and binding mode of compounds T1 and T2 towards the ERα, VEGF, and HER2 protein receptors in breast cancer cells. Data obtained from the docking study were exactly identical to that obtained from in vitro cytotoxicity assay. Conclusion: The results proved that compound T1 is an optimal anticancer agent toward breast cancer cells and the hemolysis study indicates the use of safety inside the body for compound T1. Synthesized compound T1 was most effective against MCF-7 cells compared to MDA-MB-231 cells and more effective than the reference drug tamoxifen in breast cell lines. The high cytotoxicity of compound T1 on the growth of MCF‐7 cells because T1 binds with a high degree of affinity to the estrogen and HER2 receptors, which in turn inhibits cell proliferation and induces apoptosis.

New formazan derivatives F-1 and F-2 were synthesized and tested as antioxidant and anticancer agents. Chemical structures of compounds were proved by spectroscopic methods (FT-IR, 1H-NMR and GC-Mass) and elemental analysis (CHN). The cytotoxicity activity of formazan derivatives was estimated against human breast cancer (MCF-7) cells. The synthesized compounds exhibited significant cytotoxic activity toward MCF-7 cell lines. Compound F-1 showed the highest toxicity toward MCF-7 cells. MTT assay demonstrated that 16 µg/ml of compound F-1 reduced cell growth by 88.33%, after 48 hours. Hemolysis study demonstrated that the hemolysis percentage of compounds F-1 and F-2 at (10 mg/ml) concentration was (4.05% to 4.18%), this result indicates the safety of their use inside the body. The antioxidant activity of the formazan compounds against DPPH radicals was tested in vitro. The results displayed that compound F-1 has stronger antioxidant activity than compound F-2. The new compounds were investigated in the gas phase using HyperChem software, applying semi-empirical methods and molecular mechanics. The heat of formation, binding energy, HOMO-LUMO, energy gab and dipole moment were calculated, and the results showed that compound F-1 was more stable and more polar than F-2.