Single cell combined with laser ablation ICP-MS to study cisplatinum (IV) loaded nanoparticles penetration pathways in osteosarcoma spheroids

IF 5.7 2区化学 Q1 CHEMISTRY, ANALYTICAL

Analytica Chimica Acta Pub Date : 2024-11-22 DOI:10.1016/j.aca.2024.343462

L. Gutierrez-Romero , B. Gallego , E. Blanco , U. Karst , R. Rodríguez , M. Montes-Bayon

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Abstract

Background

3D cellular structures have been considered the following step in the evaluation of drugs penetration after 2D cultures since they are more physiologically representative in cancer cell biology. Here the penetration capabilities of Pt (IV)-loaded ultrasmall iron oxide nanoparticles in 143B osteosarcoma multicellular spheroids of different sizes is conducted by a multidimensional quantitative approach. Single cell (SC) and imaging techniques (laser ablation, LA) coupled to inductively coupled plasma-mass spectrometry (ICP-MS) are used to visualize their penetration pathways and distribution in comparison to those of cisplatin.

Results

The analysis of Pt in disaggregated individual cells from spheroids shows levels of incorporation dependent on the spheroid surface to volume ratio and considerably higher than those observed for cisplatin. These results in combination with the total Pt determination in the complete spheroids reveal a preferential transcellular incorporation pathway of the Pt(IV)-loaded NPs. Elemental imaging by LA-ICP-MS shows the co—localization of Pt/Fe in hot spots at distances up to 100 μm from the spheroid surface reaching concentrations of Pt up to 200 μg g⁻¹ when exposed to Pt(IV)-loaded NPs. A more homogeneous distribution all along the spheroid is observed in the cisplatin-treated models.

Significance

The multidimensional ICP-MS based analytical methodology developed through this work offers a generalizable approach to quantitatively study the tissue penetration of nano-transported drugs to be applied in the design of nanoparticles with high accumulation at a target site.

Abstract Image

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用激光消融 ICP-MS进行单细胞组合，研究骨肉瘤球体内铂（iv）纳米粒子的渗透途径。

背景三维细胞结构被认为是继二维培养后评估药物渗透性的又一步骤，因为它们在癌细胞生物学中更具生理代表性。在此，我们采用多维定量方法研究了铂(IV)负载超小氧化铁纳米粒子在不同大小的 143B 骨肉瘤多细胞球体内的穿透能力。单细胞（SC）和成像技术（激光烧蚀，LA）与电感耦合等离子体质谱法（ICP-MS）相结合，用于观察铂的渗透途径和分布情况，并与顺铂的渗透途径和分布情况进行比较。这些结果与完整球体内的总铂测定结果相结合，揭示了负载铂(IV)的 NPs 的优先跨细胞掺入途径。通过 LA-ICP-MS 进行的元素成像显示，铂/铁共定位在距离球体表面 100 μm 的热点上，当接触到负载铂(IV)的 NPs 时，铂的浓度可达 200 μg-g-1。本研究开发的基于 ICP-MS 的多维分析方法为定量研究纳米药物的组织穿透性提供了一种可推广的方法，可用于设计在目标部位具有高蓄积性的纳米粒子。

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来源期刊

Analytica Chimica Acta 化学-分析化学

CiteScore

10.40

自引率

6.50%

发文量

1081

审稿时长

38 days

期刊介绍： Analytica Chimica Acta has an open access mirror journal Analytica Chimica Acta: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. Analytica Chimica Acta provides a forum for the rapid publication of original research, and critical, comprehensive reviews dealing with all aspects of fundamental and applied modern analytical chemistry. The journal welcomes the submission of research papers which report studies concerning the development of new and significant analytical methodologies. In determining the suitability of submitted articles for publication, particular scrutiny will be placed on the degree of novelty and impact of the research and the extent to which it adds to the existing body of knowledge in analytical chemistry.