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A robust optimization approach for the breast cancer targeted design of PEtOx-b-PLA polymersomes
Biomaterials Advances ( IF 7.9 ) Pub Date : 2021-02-16 , DOI: 10.1016/j.msec.2021.111929
Umut Can Oz , Zeynep Busra Bolat , Umut Ugur Ozkose , Sevgi Gulyuz , Berrin Kucukturkmen , Melek Parlak Khalily , Salih Ozcubukcu , Ozgur Yilmaz , Dilek Telci , Gunes Esendagli , Fikrettin Sahin , Asuman Bozkir

The equipping of nanoparticles with the peptide moiety recognizing a particular receptor, enables cell or tissue-specific targeting, therefore the optimization of the targeted nanoparticles is a key factor in the formulation design process. In this paper, we report the optimization concept of Doxorubicin encapsulating PEtOx-b-PLA polymersome formulation equipped with Peptide18, which is a breast cancer recognizing tumor homing peptide, and the unveiling of the cell-specific delivery potential. The most dominant formulation parameters, which are the polymer to Doxorubicin mass ratio (w/w) and the aqueous to organic phase ratio (v/v), were optimized using Central Composite Design (CCD) based Response Surface Methodology. The characteristics of optimum polymersome formulation were determined as the hydrodynamic diameter of 146.35 nm, the PDI value of 0.136, and the encapsulation efficiency of 57.11% and TEM imaging, which are in agreement with the DLS data, showed the spherical morphology of the polymersomes. In order to demonstrate the breast cancer-specific delivery of targeted polymersomes, the flow cytometry and confocal microscopy analyses were carried out. The targeted polymersomes were accumulated 8 times higher in AU565 cells compared to MCF10A cells and the intracellular Doxorubicin was almost 10 times higher in AU565 cells. The CCD-mediated optimized targeted polymersomes proposed in this report holds the promise of targeted therapy for breast cancer and can be potentially used for the development of novel treatments.



中文翻译:

PEtOx- b- PLA聚合物囊泡针对乳腺癌的稳健优化方法

用识别特定受体的肽部分装备纳米颗粒能够实现细胞或组织特异性靶向,因此靶向纳米颗粒的优化是制剂设计过程中的关键因素。在本文中,我们报告了阿霉素包封PEtOx- b的优化概念-配备Peptide18的PLA聚合体制剂,Peptide18是识别肿瘤归巢肽的乳腺癌,并揭示了细胞特异性递送潜力。使用基于中央复合设计(CCD)的响应表面方法优化了最主要的配方参数,即聚合物与阿霉素的质量比(w / w)和水与有机相的比率(v / v)。确定了最佳聚合物囊泡配方的特征,其流体力学直径为146.35 nm,PDI值为0.136,包封效率为57.11%,TEM成像与DLS数据一致,显示出聚合物囊泡的球形形态。为了证明乳腺癌特异性靶向聚合物的递送,进行了流式细胞术和共聚焦显微镜分析。与MCF10A细胞相比,在AU565细胞中积累的靶向多聚体要高8倍,而细胞内阿霉素在AU565细胞中则要高将近10倍。本报告中提出的CCD介导的优化的靶向聚合物囊泡有望对乳腺癌进行靶向治疗,并可潜在地用于开发新的治疗方法。

更新日期:2021-02-21
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