Three-Photon AIE Pt(II) Complexes as Cysteine-Targeting Theranostic Agents for Tumor Imaging and Chemotherapy

Abstract

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-CH 3 or L-COOEt in DMSO solution gave Lyso-Pt-CH 3 and Lyso-Pt-COOEt, respectively, which present four-coordinated square-planar geometries in mononuclear structures. Lyso-Pt-CH 3 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-CH 3 displayed a perfect signal-to-noise ratio for imaging lysosomes and for rapid detection of Cys. Using Lyso-Pt-CH 3 , 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-CH 3 might be a potential candidate as a simple and straightforward biomarker of lysosome-related Cys in vitro. Lyso-Pt-CH 3 can effectively identify tumor tissues with excessive levels of Cys. Lyso-Pt-CH 3 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.

Shining New Light on Biological Systems: Luminescent Transition Metal Complexes for Bioimaging and Biosensing Applications

“…Zhang and co-workers have developed an AIE-active platinum(II) complex ( 411 ) (Chart ) as a Cys-selective theranostic agent . The coordination of the complex with Cys induces a significant increase in the two-photon ( δ 900nm increases from 187.3 to 4,140.23 GM) and three-photon absorption cross-sections ( σ 1200nm increases from 0 to 3.41 × 10 –74 cm 6 s 2 photon –2 ) and emission intensity, which are not observed in the presence of Hcy and GSH.…”

Recent advances in aggregation-induced emission (AIE)-based chemosensors for the detection of organic small molecules

“…3b). 104 Lastly, A30 , A31 , A32 are chemosensors with Au cores. Hao's group designed A30 which contains GSH-Au NC while Xu's group designed A31 with Au@Ag NC.…”