A novel self-assembled nanoplatform based on retrofitting poloxamer 188 for triple-negative breast cancer targeting treatment

IF 4.7 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Xueyan Hou , Yalin Guan , Sisi He , Zeqing Wu , Jintao Bai , Jingjing Xu , Jingwen Wang , Suyue Xu , Huiqing Zhu , Yanyan Yin , Xue Yang , Yongli Shi
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Abstract

Poloxamer 188 is a widely used pharmaceutical excipient, which can be found in a variety of drug formulations. In this study, a novel self-assembled nanoplatform was developed for active targeting of folate receptor-overexpressing triple-negative breast cancer. This platform, FPP NPs, was prepared by the retrofitted poloxamer 188 derivatives, resulting in nanoparticles with an appropriate size (< 100 nm), good stability, and satisfactory biocompatibility. Cellular uptake and in vivo distribution studies showed that the FPP NPs had strong tumor cell uptake and active targeting capabilities. Furthermore, docetaxel (DTX) was loaded into FPP NPs in this research. The resulting DTX/FPP NPs exhibited high drug encapsulation efficiency and drug loading capacity, and could rapidly release DTX under slightly acidic conditions, significantly increasing the antitumor activity of the encapsulated drug both in vitro and in vivo. In addition, DTX/FPP NPs could significantly decrease the hepatotoxicity and nephrotoxicity of DTX. Therefore, this drug delivery nanoplatform, based on retrofitted poloxamer 188 with self-assembly properties in aqueous solution and active targeting capabilities to tumors, may provide a promising approach for targeted treatment of triple-negative breast cancer.

Abstract Image

一种新型的基于泊洛沙姆188的自组装纳米平台,用于三阴性乳腺癌症靶向治疗。
泊洛沙姆188是一种广泛使用的药用赋形剂,可以在各种药物制剂中找到。本研究开发了一种新型的自组装纳米平台,用于主动靶向过表达叶酸受体的癌症三阴性。该平台FPP NPs是由改性的泊洛沙姆188衍生物制备的,产生了具有适当尺寸(<100nm)、良好稳定性和令人满意的生物相容性的纳米颗粒。细胞摄取和体内分布研究表明,FPP-NP具有较强的肿瘤细胞摄取和主动靶向能力。此外,在本研究中,多西他赛(DTX)被装载到FPP NP中。所得到的DTX/FPP NPs表现出高的药物包封效率和载药能力,并且可以在微酸性条件下快速释放DTX,显著提高了包封药物的体内外抗肿瘤活性。此外,DTX/FPP NPs可显著降低DTX的肝毒性和肾毒性。因此,该药物递送纳米平台基于在水溶液中具有自组装性质和对肿瘤的主动靶向能力的改良泊洛沙姆188,可能为靶向治疗癌症三阴性提供一种有前途的方法。
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来源期刊
CiteScore
7.70
自引率
3.90%
发文量
410
审稿时长
36 days
期刊介绍: Chemico-Biological Interactions publishes research reports and review articles that examine the molecular, cellular, and/or biochemical basis of toxicologically relevant outcomes. Special emphasis is placed on toxicological mechanisms associated with interactions between chemicals and biological systems. Outcomes may include all traditional endpoints caused by synthetic or naturally occurring chemicals, both in vivo and in vitro. Endpoints of interest include, but are not limited to carcinogenesis, mutagenesis, respiratory toxicology, neurotoxicology, reproductive and developmental toxicology, and immunotoxicology.
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