Monitoring Molecular Uptake and Cancer Cells' Response by Development of Quantitative Drug Derivative Probes for Chemical Imaging.

IF 6.7 1区化学 Q1 CHEMISTRY, ANALYTICAL

Analytical Chemistry Pub Date : 2025-09-09 DOI:10.1021/acs.analchem.5c00863

Pei-Hsuan Hsieh,Shu-An Hsieh,Craig Richard,Kannanganattu V Prasanth,Jared L Anderson,Rohit Bhargava

{"title":"Monitoring Molecular Uptake and Cancer Cells' Response by Development of Quantitative Drug Derivative Probes for Chemical Imaging.","authors":"Pei-Hsuan Hsieh,Shu-An Hsieh,Craig Richard,Kannanganattu V Prasanth,Jared L Anderson,Rohit Bhargava","doi":"10.1021/acs.analchem.5c00863","DOIUrl":null,"url":null,"abstract":"Infrared (IR) spectroscopic imaging combines the molecular specificity of vibrational spectroscopy with imaging capabilities of microscopy, potentially allowing for simultaneous quantitative observations of drugs and cellular response. However, accurately quantifying drug concentration within changing cells is complicated by the overlap between exogenous molecules' and native cellular spectra. Here, we address this challenge by developing a derivative of the widely used chemotherapeutic doxorubicin as a spectral bioprobe (DOX-IR) using a strongly absorbing metal-carbonyl moiety [(Cp)Fe(CO)2]. The developed protocol for synthesis is validated by complete spectral characterization of DOX-IR, and an IR calibration curve is obtained for the two distinguishable peaks within the biosilent spectral region. The strong absorbance allowed cellular uptake of DOX-IR to be quantified using routinely available IR microscopes without any modifications. The capability to quantify drug compounds in a nondestructive and high-throughput manner using IR spectroscopic imaging provides straightforward analysis without perturbing the sample.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"130 1","pages":""},"PeriodicalIF":6.7000,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Analytical Chemistry","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1021/acs.analchem.5c00863","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, ANALYTICAL","Score":null,"Total":0}

引用次数: 0

Abstract

Infrared (IR) spectroscopic imaging combines the molecular specificity of vibrational spectroscopy with imaging capabilities of microscopy, potentially allowing for simultaneous quantitative observations of drugs and cellular response. However, accurately quantifying drug concentration within changing cells is complicated by the overlap between exogenous molecules' and native cellular spectra. Here, we address this challenge by developing a derivative of the widely used chemotherapeutic doxorubicin as a spectral bioprobe (DOX-IR) using a strongly absorbing metal-carbonyl moiety [(Cp)Fe(CO)2]. The developed protocol for synthesis is validated by complete spectral characterization of DOX-IR, and an IR calibration curve is obtained for the two distinguishable peaks within the biosilent spectral region. The strong absorbance allowed cellular uptake of DOX-IR to be quantified using routinely available IR microscopes without any modifications. The capability to quantify drug compounds in a nondestructive and high-throughput manner using IR spectroscopic imaging provides straightforward analysis without perturbing the sample.

查看原文本刊更多论文

开发用于化学成像的定量药物衍生物探针监测分子摄取和癌细胞反应。

红外（IR）光谱成像结合了振动光谱的分子特异性和显微镜的成像能力，有可能同时定量观察药物和细胞反应。然而，由于外源分子和原生细胞光谱的重叠，准确定量变化细胞内的药物浓度变得复杂。在这里，我们通过开发广泛使用的化疗药物阿霉素的衍生物作为光谱生物探针（DOX-IR）来解决这一挑战，该衍生物使用强吸收金属羰基部分[(Cp)Fe(CO)2]。通过完整的DOX-IR光谱表征验证了所建立的合成方案，并在生物沉默光谱区域内获得了两个可区分峰的红外校准曲线。强吸光度允许使用常规可用的红外显微镜对DOX-IR的细胞摄取进行量化，而无需任何修改。使用红外光谱成像以非破坏性和高通量的方式定量药物化合物的能力提供了直接的分析，而不会干扰样品。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Analytical Chemistry 化学-分析化学

CiteScore

12.10

自引率

12.20%

发文量

1949

审稿时长

1.4 months

期刊介绍： Analytical Chemistry, a peer-reviewed research journal, focuses on disseminating new and original knowledge across all branches of analytical chemistry. Fundamental articles may explore general principles of chemical measurement science and need not directly address existing or potential analytical methodology. They can be entirely theoretical or report experimental results. Contributions may cover various phases of analytical operations, including sampling, bioanalysis, electrochemistry, mass spectrometry, microscale and nanoscale systems, environmental analysis, separations, spectroscopy, chemical reactions and selectivity, instrumentation, imaging, surface analysis, and data processing. Papers discussing known analytical methods should present a significant, original application of the method, a notable improvement, or results on an important analyte.