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载紫杉醇的抗 EGFR 锚定 PLGA 纳米粒用于三阴性乳腺癌的治疗:体外和体内抗癌活性。

Anti-EGFR anchored paclitaxel loaded PLGA nanoparticles for the treatment of triple negative breast cancer. In-vitro and in-vivo anticancer activities.

机构信息

Department of Pharmaceutical Technology, Faculty of Pharmacy, Asian Institute of Medical Science and Technology (AIMST) University, Kedah, Malaysia.

School of Pharmacy, Medical Biology Centre, Queen's University Belfast, Northern Ireland, UK.

出版信息

PLoS One. 2018 Nov 8;13(11):e0206109. doi: 10.1371/journal.pone.0206109. eCollection 2018.

Abstract

The aim of the present study is to analyze the viability of anti-EGFR anchored immunonanoparticle (INP) bearing Paclitaxel (PTX) to specifically bind the EGFR protein on the TNBC cells. The NP was prepared by nanoprecipitation and characterized the particle size, charge, entrapment of drug and release of it. The anti-EGFR anchored and the integrity was confirmed by SDS-PAGE. Cytotoxicity and NPs cellular uptake was analyzed with MDA-MB-468 type cancer cells and the EGFR expression was confirmed by PCR, qualitatively and quantitatively. The in-vivo antitumor activity of INP was determined by using athymic mice model and targeting efficiency was measured by calculating the PTX accumulation in the tumor plasma. The prepared INP with the size of 336.3 nm and the charge of -3.48 mV showed sustained drug release upto 48 h. The INP showed significant reduction of cancer cell viability of 10.6% for 48 h with 93 fold higher PTX accumulation in the tumor plasma compared with NPs. Based on these reports, we recommend that anti-EGFR anchored PTX loaded NP may have the ability to target the TNBC cells and improve the therapeutic action and subsidize the side effects of PTX for the treatment of TNBC.

摘要

本研究旨在分析载紫杉醇(PTX)的抗 EGFR 锚定免疫纳米颗粒(INP)的可行性,以特异性结合 TNBC 细胞上的 EGFR 蛋白。NP 通过纳米沉淀法制备,并对粒径、电荷、药物包封率和释放进行了表征。通过 SDS-PAGE 确认了抗 EGFR 锚定和完整性。用 MDA-MB-468 型癌细胞分析了细胞毒性和 NPs 的细胞摄取,并通过 PCR 对 EGFR 的表达进行了定性和定量分析。通过使用无胸腺小鼠模型确定了 INP 的体内抗肿瘤活性,并通过计算肿瘤血浆中的 PTX 积累来测量靶向效率。制备的 INP 粒径为 336.3nm,电荷为-3.48mV,显示出长达 48 小时的持续药物释放。INP 显示出对癌细胞活力的显著降低,48 小时内降低了 10.6%,与 NPs 相比,肿瘤血浆中的 PTX 积累增加了 93 倍。基于这些报告,我们建议载有 PTX 的抗 EGFR 锚定 NP 可能具有靶向 TNBC 细胞的能力,从而提高治疗作用,并减轻 PTX 治疗 TNBC 的副作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3694/6224030/d9287a249efe/pone.0206109.g001.jpg

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