Investigation of the Therapeutic Effects of Palbociclib Conjugated Magnetic Nanoparticles on Different Types of Breast Cancer Cell Lines.

IF 2.3 4区医学 Q3 BIOPHYSICS Cellular and molecular bioengineering Pub Date : 2023-01-07 eCollection Date: 2023-04-01 DOI:10.1007/s12195-022-00758-4

Maryam Parsian, Pelin Mutlu, Negar Taghavi Pourianazar, Serap Yalcin Azarkan, Ufuk Gunduz

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引用次数: 1

Abstract

Introduction: Drug targeting and controlled drug release systems in cancer treatment have many advantages over conventional chemotherapy in terms of limiting systemic toxicity, side effects, and overcoming drug resistance.

Methods and results: In this paper, fabricating nanoscale delivery system composed of magnetic nanoparticles (MNPs) covered with poly-amidoamine (PAMAM) dendrimers and using its advantages were fully used to help the chemotherapeutic drug, Palbociclib, effectively reach tumors, specifically and stay stable in the circulation longer. In order to determine whether conjugate selectivity can be increased for the specific drug type, we have reported different strategies for loading and conjugation of Palbociclib to different generations of magnetic PAMAM dendrimers. The best method leading to the highest amount of Palbociclib conjugation was chosen, and the characterization of the Palbociclib conjugated dendrimeric magnetic nanoparticles (PAL-DcMNPs) were performed. In vitro pharmacological activity of the conjugation was demonstrated by measuring the cell viability and lactate dehydrogenase (LHD) release. Obtained results indicated that PAL-DcMNPs treatment of the breast cancer cell lines, leads to an increase in cell toxicity compared to free Palbociclib. The observed effects were more evident for MCF-7 cells than for MDA-MB231 and SKBR3 cells, considering that viability decreased to 30% at 2.5 µM treatment of PAL-DcMNPs at MCF-7 cells. Finally, in Palbociclib and PAL-DcMNPs treated breast cancer cells, the expression levels of some pro-apoptotic and drug resistance related genes were performed by RT-PCR analysis.

Conclusion: Our knowledge indicates that the proposed approach is novel, and it can provide new insight into the development of Palbociclib targeting delivery system for cancer treatment.

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研究Palbociclib共轭磁性纳米粒子对不同类型乳腺癌细胞系的治疗作用

简介：药物靶向和药物控释系统在癌症治疗中与传统化疗相比具有许多优势：癌症治疗中的药物靶向和药物控释系统与传统化疗相比，在限制全身毒性、副作用和克服耐药性等方面具有许多优势：本文充分发挥磁性纳米颗粒（MNPs）包覆聚氨基胺（PAMAM）树枝状聚合物的优势，制作了纳米级给药系统，帮助化疗药物帕博西尼（Palbociclib）有效、特异性地到达肿瘤，并在循环中保持更长时间的稳定。为了确定能否提高共轭物对特定药物类型的选择性，我们报告了将 Palbociclib 装载和共轭到不同代磁性 PAMAM 树枝状分子的不同策略。我们选择了能获得最高Palbociclib共轭量的最佳方法，并对Palbociclib共轭树枝状聚合物磁性纳米颗粒（PAL-DcMNPs）进行了表征。通过测定细胞活力和乳酸脱氢酶（LHD）释放量，证明了该共轭物的体外药理活性。结果表明，与游离的 Palbociclib 相比，PAL-DcMNPs 处理乳腺癌细胞系会导致细胞毒性增加。与 MDA-MB231 和 SKBR3 细胞相比，在 MCF-7 细胞中观察到的影响更为明显，因为在 MCF-7 细胞中处理 2.5 µM 的 PAL-DcMNPs 时，细胞活力下降了 30%。最后，在Palbociclib和PAL-DcMNPs处理的乳腺癌细胞中，通过RT-PCR分析了一些促凋亡基因和耐药性相关基因的表达水平：我们的研究表明，所提出的方法是新颖的，它能为开发用于癌症治疗的帕博西尼靶向递送系统提供新的见解。

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来源期刊

Cellular and molecular bioengineering 生物-生物物理

CiteScore

5.60

自引率

3.60%

发文量

审稿时长

>12 weeks

期刊介绍： The field of cellular and molecular bioengineering seeks to understand, so that we may ultimately control, the mechanical, chemical, and electrical processes of the cell. A key challenge in improving human health is to understand how cellular behavior arises from molecular-level interactions. CMBE, an official journal of the Biomedical Engineering Society, publishes original research and review papers in the following seven general areas: Molecular: DNA-protein/RNA-protein interactions, protein folding and function, protein-protein and receptor-ligand interactions, lipids, polysaccharides, molecular motors, and the biophysics of macromolecules that function as therapeutics or engineered matrices, for example. Cellular: Studies of how cells sense physicochemical events surrounding and within cells, and how cells transduce these events into biological responses. Specific cell processes of interest include cell growth, differentiation, migration, signal transduction, protein secretion and transport, gene expression and regulation, and cell-matrix interactions. Mechanobiology: The mechanical properties of cells and biomolecules, cellular/molecular force generation and adhesion, the response of cells to their mechanical microenvironment, and mechanotransduction in response to various physical forces such as fluid shear stress. Nanomedicine: The engineering of nanoparticles for advanced drug delivery and molecular imaging applications, with particular focus on the interaction of such particles with living cells. Also, the application of nanostructured materials to control the behavior of cells and biomolecules.