Doxorubicin delivery systems with an acetylacetone-based block in cholesterol-terminated copolymers: Diverse activity against estrogen-dependent and estrogen-independent breast cancer cells

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Chemistry and Physics of Lipids Pub Date : 2022-07-01 DOI:10.1016/j.chemphyslip.2022.105194

Paweł Misiak , Katarzyna Niemirowicz-Laskowska , Iwona Misztalewska-Turkowicz , Karolina H. Markiewicz , Przemysław Wielgat , Halina Car , Agnieszka Z. Wilczewska

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引用次数: 2

Abstract

The study presents the synthesis of original cholesterol-terminated copolymers comprising acetylacetone-based (AcacI) and N-isopropylacrylamide (NIPAAm) units with a varied arrangement (block and random copolymers). The nanoprecipitation method was used to form empty and doxorubicin-loaded polymeric nanoparticles (PNPs) from these copolymers, which were further studied in terms of their physicochemical and biological properties. Unexpectedly, it was revealed that even empty PNPs are effective against breast cancer cells, specifically towards estrogen-dependent MCF-7 cell line. The anti-cancer efficacy was further improved when a low dose of doxorubicin was introduced to the tested systems. It was shown that the proposed carriers modulate doxorubicin (DOX) compatibility with representatives of normal cells, including immune cells, cardiomyocyte cells, and fibroblasts, and reduce side effects associated with standard chemotherapy. The use of these carriers might be a strategy leading to enhancement of DOX activity in cancer cells which develop resistance through decreased drug penetration or drug efflux.

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阿霉素输送系统与乙酰丙酮为基础阻断胆固醇端共聚物:对雌激素依赖性和雌激素非依赖性乳腺癌细胞的不同活性

本研究提出了由乙酰丙酮基(AcacI)和n -异丙基丙烯酰胺(NIPAAm)单元组成的原始胆固醇端共聚物的合成，这些共聚物具有不同的排列(嵌段和无规则共聚物)。采用纳米沉淀法将这些共聚物制备成空的和负载阿霉素的聚合物纳米颗粒(PNPs)，并进一步研究了它们的物理化学和生物学性质。出乎意料的是，即使是空的PNPs也对乳腺癌细胞有效，特别是对雌激素依赖性MCF-7细胞系。当低剂量的阿霉素被引入测试系统时，抗癌效果进一步提高。研究表明，拟议的载体调节了阿霉素(DOX)与正常细胞的相容性，包括免疫细胞、心肌细胞和成纤维细胞，并减少了与标准化疗相关的副作用。使用这些载体可能是一种通过减少药物渗透或药物外排而产生耐药性的癌细胞中DOX活性增强的策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Chemistry and Physics of Lipids 生物-生化与分子生物学

CiteScore

7.60

自引率

2.90%

发文量

审稿时长

40 days

期刊介绍： Chemistry and Physics of Lipids publishes research papers and review articles on chemical and physical aspects of lipids with primary emphasis on the relationship of these properties to biological functions and to biomedical applications. Accordingly, the journal covers: advances in synthetic and analytical lipid methodology; mass-spectrometry of lipids; chemical and physical characterisation of isolated structures; thermodynamics, phase behaviour, topology and dynamics of lipid assemblies; physicochemical studies into lipid-lipid and lipid-protein interactions in lipoproteins and in natural and model membranes; movement of lipids within, across and between membranes; intracellular lipid transfer; structure-function relationships and the nature of lipid-derived second messengers; chemical, physical and functional alterations of lipids induced by free radicals; enzymatic and non-enzymatic mechanisms of lipid peroxidation in cells, tissues, biofluids; oxidative lipidomics; and the role of lipids in the regulation of membrane-dependent biological processes.