Journal
ANALYTICAL CHEMISTRY
Volume 94, Issue 42, Pages 14769-14777Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.analchem.2c03431
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Funding
- National Natural Science Foundation of China [21871003, 21701160, 51772002]
- Anhui University [S020118002/073, S020118002/026]
- Nature Science Foundation of Anhui Province [1908085MB30, 2008085QB52]
- National Major Scientific Instrument and Equipment Development Project [21927814]
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In this study, a series of three-photon fluorescent Pt(II) complexes targeting a tumor-associated biothiol, cysteine (Cys), were synthesized to detect Cys without interference from other intracellular proteins. The fluorescence response of Cys was significantly improved by regulating the recognition units in the probes. The synthesized complex, Lyso-Pt-CH3, showed strong three-photon absorption cross section (3PA) only in the presence of Cys, making it a potential biomarker for lysosome-related Cys in vitro. This work provides a novel strategy for the rational design of controllably activated and Cys-targeted Pt(II) anticancer prodrugs for clinical diagnosis and treatment.
Herein, we have synthesized a series of three-photon fluorescent Pt(II) complexes targeting a tumor-associated biothiol, cysteine (Cys), which allows it to be detected without any interference from other intracellular proteins. We focused on how to significantly improve the fluorescence response of Cys via regulating the recognition units in probes. The reaction of K2PtCl4 with L-CH3 or L-COOEt in DMSO solution gave Lyso-Pt-CH3 and Lyso-Pt-COOEt, respectively, which present four-coordinated square-planar geometries in mononuclear structures. Lyso-Pt-CH3 consists of a Cys aptamer labeled with typical aggregation-induced emission (AIE) characteristics, which shows strong three-photon absorption cross section (3PA) only in the presence of Cys. It was found that Lyso-Pt-CH3 displayed a perfect signal-to-noise ratio for imaging lysosomes and for rapid detection of Cys. Using Lyso-Pt-CH3, Cys-related cellular mechanisms were proposed. We confirm that cystine (Cyss) could be absorbed in cells through cystine/glutamate antiporters (system xc-) and is then converted to Cys under the effect of enzymes. All of these suggest that Lyso-Pt-CH3 might be a potential candidate as a simple and straightforward biomarker of lysosome-related Cys in vitro. Lyso-Pt-CH3 can effectively identify tumor tissues with excessive levels of Cys. Lyso-Pt-CH3 also showed excellent antitumor activity than cisplatin. This work provides a novel strategy for the rational design of controllably activated and Cys-targeted Pt(II) anticancer prodrugs for clinical diagnosis and treatment.
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