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载他莫昔芬的促红细胞生成素包裹给药系统增强抗乳腺癌活性。

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

机构信息

Institute of Bioscience, Universiti Putra Malaysia, UPM Serdang, Selangor, Malaysia.

Faculty of Veterinary Medicine, Universiti Putra Malaysia, UPM Serdang, Selangor, Malaysia.

出版信息

PLoS One. 2019 Jul 10;14(7):e0219285. doi: 10.1371/journal.pone.0219285. eCollection 2019.

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.

摘要

纳米医学是医学领域的一个新兴领域,特别是在癌症治疗方面。纳米结构脂质载体(NLC)已被证明是一种用于传递他莫昔芬(TAM)的良好纳米颗粒载体。在这项研究中,使用 EPO 作为乳腺癌组织细胞上 EPO 受体(EpoRs)的同源配体,开发了载有他莫昔芬的红细胞生成素包被的纳米结构脂质载体(EPO-TAMNLC),以增强 TAM 的抗癌特性和靶向性。使用载有他莫昔芬的 NLC(TAMNLC)进行比较。LA7 细胞和 LA7 细胞诱导的大鼠乳腺肿瘤被用作研究模型。免疫细胞化学染色显示 LA7 细胞表达雌激素受体(ERs)和 EpoRs。EPO-TAMNLC 和 TAMNLC 以剂量和时间依赖的方式显著(p<0.05)抑制 LA7 的增殖。EPO-TAMNLC 诱导 LA7 细胞凋亡和 G0/G1 细胞周期停滞。两种药物递送系统均显示出抗乳腺肿瘤特性。在静脉剂量为 5mg/kg 体重时,EPO-TAMNLC 和 TAMNLC 对大鼠没有毒性,表明两者均为安全的治疗化合物。总之,EPO-TAMNLC 不仅是一种独特的药物递送系统,因为具有双重药物加载特性,而且对于 ERs 和 EpoRs 阳性的乳腺癌组织具有潜在的高度特异性。将 TAM 掺入带有和不带有 EPO 涂层的 NLC 中,显著(p<0.05)提高了药物载体在治疗乳腺肿瘤中的特异性和安全性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0472/6619690/d1c5336a5e3f/pone.0219285.g001.jpg

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