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

Chaw Yee Beh,Jhi Biau Foo,Chee Wun How,Abdul Rahman Omar,Abdullah Rasedee,Jia Ning Foong,Latifah Saiful Yazan,Gayathri Thevi Selvarajah,Irina V Lebedeva

doi:10.1371/journal.pone.0219285

Chaw Yee Beh, Jhi Biau Foo + Show 7 more

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https://doi.org/10.1371/journal.pone.0219285

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Abstract

Nanomedicine is an emerging area in the medical field, particularly in the treatment of cancers. Nanostructured lipid carrier (NLC) was shown to be a good nanoparticulated carrier for the delivery of tamoxifen (TAM). In this study, the tamoxifen-loaded erythropoietin-coated nanostructured lipid carriers (EPO-TAMNLC) were developed to enhance the anti-cancer properties and targetability of TAM, using EPO as the homing ligand for EPO receptors (EpoRs) on breast cancer tissue cells. Tamoxifen-loaded NLC (TAMNLC) was used for comparison. The LA7 cells and LA7 cell-induced rat mammary gland tumor were used as models in the study. Immunocytochemistry staining showed that LA7 cells express estrogen receptors (ERs) and EpoRs. EPO-TAMNLC and TAMNLC significantly (p<0.05) inhibited proliferation of LA7 in dose- and time-dependent manner. EPO-TAMNLC induced apoptosis and G0/G1 cell cycle arrest of LA7 cells. Both drug delivery systems showed anti-mammary gland tumor properties. At an intravenous dose of 5 mg kg-1 body weight, EPO-TAMNLC and TAMNLC were not toxic to rats, suggesting that both are safe therapeutic compounds. In conclusion, EPO-TAMNLC is not only a unique drug delivery system because of the dual drug-loading feature, but also potentially highly specific in the targeting of breast cancer tissues positive for ERs and EpoRs. The incorporation of TAM into NLC with and without EPO coat had significantly (p<0.05) improved specificity and safety of the drug carriers in the treatment of mammary gland tumors.

Highlights

Current strategies most often used to combat breast cancers include radiation, hormonal, and targeted therapy, adjuvant chemotherapies are always incorporated to increase the rate of patient survival [1]
Thimerosal, sorbitol, bovine serum albumin (BSA), dimethyl sulfoxide (DMSO), Tamoxifen free base, 4’,6-diamidino-2-phenylindole (DAPI), propidium iodide (PI), ribonuclease A (Rnase A), thiazolyl blue tetrazolium bromide (MTT), Harris’s haematoxylin and eosin (H&E), ketamine hydrochloride, xylazine hydrochloride, horse serum, epidermal growth factor (EGF), hydrocortisone and insulin were purchased from Sigma-Aldrich (St Loius, MO, USA)
Since EPO receptors (EpoRs) are highly expressed in breast cancers [12, 29], EPO coating on EPO-Tamoxifen-loaded nanostructured lipid carriers (NLCs) (TAMNLC) surfaces serve as the ligand in the binding of the nanoparticles to EpoR on the breast cancer cells [15]

Summary

Introduction

Current strategies most often used to combat breast cancers include radiation, hormonal, and targeted therapy, adjuvant chemotherapies are always incorporated to increase the rate of patient survival [1]. The most commonly used drugs in the treatment of breast cancers, doxorubicin, tamoxifen citrate, paclitaxel, and etoposide, are fraught with lack of specificity. Anti-mammary gland cancer activities of tamoxifen-loaded erythropoietin-coated drug delivery system and induction of drug resistance [2]. The development of resistance to these drugs may be the result of cancer cell heterogeneity, DNA damage repair mechanism, drug efflux, and cell death inhibition [3]. Most anticancer drugs are administered orally and their therapeutic concentrations in blood are governed by the efficiency of gastrointestinal tract absorption. Oral drugs administrations often need high doses to achieve therapeutic concentrations in blood

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