Development of erythropoietin receptor-targeted drug delivery system against breast cancer using tamoxifen-loaded nanostructured lipid carriers

Abstract

Tamoxifen (TAM) has been used in the treatment of breast cancers and is supplemented with erythropoietin (EPO) to alleviate the cancer-related anemia. The purported deleterious effects caused by the use of EPO with chemotherapeutic agents in the treatment of cancer-related anemia vary across studies and remain controversial. The use of nanoparticles as a drug delivery system has the potential to improve the specificity of anticancer drugs. In this study, we simultaneously incorporated two pharmacological active ingredients in one nanocarrier to develop EPO-conjugated TAM-loaded lipid nanoparticles (EPO-TAMNLC), a targeted delivery system, to enhance the cytotoxic activity while reducing the side effects of the ingredients. The effect of temperature in modulating the thermodynamic parameters associated with the binding of EPO and TAMNLC was assessed using isothermal titration calorimetry, while the unfolding of EPO structure was determined using fluorescence-quenching approach. The association efficiency of EPO and TAMNLC was 55.43%. Unlike binding of albumin to TAMNLC, the binding of EPO to TAMNLC occurred through endothermic and entropy-driven reaction. The EPO-TAMNLC formulation was stable because of the hydrophobic interaction and the high free energy, suggesting the spontaneity of the interactions between EPO and TAMNLC. The EPO-TAMNLC enhanced the in vitro cytotoxicity of TAM to MCF-7 cells. The EPO surface-functionalized TAMNLC could sequentially deliver EPO and TAM as well as improving site-specific delivery of these therapeutic compounds.

Erythropoietin Potentiates the Anti-Proliferative Effect of Tamoxifen in Ovarian Adenocarcinoma A2780 Cells

“…25 Recently, EPO-conjugated TAM-loaded lipid nanoparticles enhanced the in vitro cytotoxicity of TAM to MCF-7 cells and showed that EPOR expressed on cancer cells is a potential receptor for drug-targeted therapy. 26 Although EPOR has been detected with specific A82 antibody in A2780 cells (Fig. 1B), neither the effect of 10 IU/ ml nor the effect of 100 IU/ml of EPO on the proliferation of these cells was observed.…”

Enhanced anti-mammary gland cancer activities of tamoxifen-loaded erythropoietin-coated drug delivery system

“…Structurally, EPO-TAMNLC comprises of loaded TAM within the core and a coating of EPO on the surface of the nanoparticles. Since EpoR are highly expressed in breast cancers [12, 29], EPO coating on EPO-TAMNLC surfaces serve as the ligand in the binding of the nanoparticles to EpoR on the breast cancer cells [15]. EPO does not compromise the efficaciousness of breast cancer chemotherapeutics [30, 31].…”

“…EPO does not compromise the efficaciousness of breast cancer chemotherapeutics [30, 31]. In fact, in an early study, we showed that EPO-TAMNLC and TAMNLC had greater antiproliferative effect on MCF-7 cells than TAM [15].…”

“…Based on these observations, we developed the EPO-coated TAM-loaded lipid nanoparticles (EPO-TAMNLC) to enhance the anti-tumor effect of TAM. EPO-TAMNLC showed greater in vitro cytotoxicity than TAM on MCF-7 cells [15]. In the current study, the effects of EPO-TAMNLC and TAMNLC on LA7 cells and LA7 cell-induced rat mammary gland tumor were determined.…”

Buparvaquone nanostructured lipid carrier development: physicochemical and <i>in vitro</i> leishmanicidal performances

“…Figure 7): higher encapsulation efficiency, better control of drug release and lower drug expulsion during product storageSÁNCHEZ-LÓPEZ et al, 2017). Thus, these nanocarriers have been used in the preparation of low water solubility drugs to increase the efficacy and reduce toxicity(BEH et al, 2017) Figure 1.6. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) structures and NLC advantages.…”