Fabrication of red-emissive ZIF-8@QDs nanoprobe with improved fluorescence based on assembly strategy for enhanced biosensing

Highlights

• The red-emissive ZIF-8@QDs nanoprobe was prepared based on assembly strategy.

• The combination of QDs and ZIF-8 prevented QDs aggregation and improved QDs fluorescence.

• The ZIF-8@QDs nanoprobe had the advantages of MOFs that can selectively accumulate analytes.

• The improved fluorescence and accumulation effect of ZIF-8@QDs amplified the sensing signal.

• The ZIF-8@QDs nanoprobe achieved multiple targets detection with enhanced sensitivity.

Abstract

In this study, brightly red-emissive nanoprobe (ZIF-8@QDs) was constructed based on the assembly between Hg-ZnSe QDs and zeolitic imidazolate framework-8 (ZIF-8) for ultrasensitive determination of glutathione S-transferase (GST). The ZIF-8@QDs nanoprobe not only enhanced the fluorescence of QDs, but also had the advantages of MOFs, which largely improved the analytical sensitivity. Cu²⁺ could be selectively enriched on the surface of ZIF-8@QDs, and resulting in its fluorescence quenching. However, in the presence of glutathione (GSH), ZIF-8@QDs fluorescence was recovered due to the strong affinity between Cu²⁺ and GSH. Moreover, with the catalysis of GST, GSH would react with 1-chloro-2,4-dinitrobenzene (CDNB) to form an adduct that could not coordinate with Cu²⁺, leading to ZIF-8@QDs fluorescence quenched again. Hence, a simple and sensitive "off-on-off" fluorescent sensing platform was fabricated for the determination of GST with a wide linear range of 0.05–1.2 mU/L. Moreover, the LOD of the ZIF-8@QDs nanoprobe for GST was 0.014 mU/L, which was improved about 15 times compared with QDs nanoprobe. This assay provided a promising method to design and synthesize high-performance MOF-based nanoprobe for in vitro diagnosis and possessed great potential in the field of bioinformatics and clinical medicine.

Introduction

Metal–organic frameworks (MOFs), as a family of highly ordered porous materials, are prepared by assembling metallic ions and organic bridge ligands [1]. In the past decades, MOFs have been diligently investigated for diversified applications including energy storage, heterogeneous catalysis, separation, and chemical sensing due to their intriguing characteristics such as tunable shapes and pore sizes, structural diversity, and high thermal stability [2], [3], [4]. Currently, with the development of MOFs and their applications, more researchers have been focusing on the combination of MOFs and other attractive nanomaterials to construct the MOF-based nanocomposites. The MOF-based nanocomposites not only prevent guest nanomaterials from aggregation, but also improve the properties of the nanomaterials. Due to the superior properties of the MOF-based nanocomposites, they are widely used in the fields of drug delivery, catalysis, and sensing [5], [6], [7], [8]. As one of the most interesting representatives of MOFs, zeolitic imidazolate framework-8 (ZIF-8) has the outstanding features including high porosity, good water dispersion, large surface area, and simplicity of synthesis [9]. Based on these advantages, researchers have constructed various MOF-based nanoprobes by combining ZIF-8 with fluorescent nanomaterials including quantum dots (QDs), fluorescent dyes, carbon dots (CDs), and metal nanoclusters [10], [11], [12]. These MOF-based nanoprobes were applied to the determination of metal ions, small molecules, and DNA with satisfactory results [13], [14]. Nevertheless, the reports of the MOF-based nanoprobes that can simultaneously improve nanomaterials fluorescence and detection sensitivity were relatively limited, which were urgently demanded to further investigation.

Semiconductor quantum dots (QDs) have attracted considerable attention in the field of biosensing due to their attractive characteristics such as tunable and narrow emission spectra, broad absorption range, and high photostability [15], [16], [17]. Particularly, zinc selenide quantum dots (ZnSe QDs), as a kind of Cd-free QDs, have been gaining much attention for several years because of their low toxicity and excellent biocompatibility [18]. Nevertheless, the fluorescence emission of ZnSe QDs are mainly focused on the regions of ultraviolet and blue, which inevitably suffers from the interference of autofluorescence in matrix and thus limits their applications in complex biological samples. The doping of metal heteroatoms can effectively adjust the emission wavelength of ZnSe QDs and enhance the luminescence properties of ZnSe QDs [19]. Previously, our group successfully synthesized Hg-ZnSe QDs with red emission and good stability by a facile method [20]. However, the Hg-ZnSe QDs emission quantum yield was relatively low, which needs to further investigation to improve their luminescence performance. Previous studies have confirmed that the porous structure of MOFs can not only improve the properties of nanomaterials, but also prevent the aggregation effect of nanomaterials. Thus, the combination of Hg-ZnSe QDs and MOFs might be an effective approach to improve their fluorescence performance.

Glutathione S-transferases (GSTs) are a class of detoxifying enzymes ubiquitous in organisms, playing an important role in almost all organs, especially liver [21], [22], [23]. The main function of GSTs is to catalyze glutathione (GSH) to react with electrophilic organic compounds such as endogenous superoxide radicals or toxic metabolites to form water-soluble derivatives that are excreted through urine or bile [24]. Thus, the presence of GSTs with appropriate concentration can protect the organs and tissues against damage. In addition, GSTs are often overexpressed in tumor tissues and are considered as a significant marker of various tumors, such as breast, ovarian, lung, and gastric cancers [25]. Therefore, the development of effective approaches for GSTs activity is crucial for the early diagnosis of diseases and the screening of anticancer drugs. In the past few decades, some conventional methods have been investigated for GSTs activity analysis, including electrochemistry [26], mass spectrometry [27], colorimetry [28], and fluorimetry [29]. However, these methods are always suffered from some drawbacks, including large sample consumption, time-consuming, low sensitivity, and cumbersome preparation process. To address these issues, it is urgently required to develop a fast, convenient and sensitive approach for GSTs activity assay.

Inspired by previous pioneering works, herein, a MOF-based nanoprobe (ZIF-8@QDs) with strong red emission was fabricated by the assembly between quantum dots (QDs) and ZIF-8 for ultrasensitive detection of glutathione S-transferase (GST) activity. To our surprise, the fluorescence of QDs could be largely improved after assembly between QDs and ZIF-8. More importantly, the prepared ZIF-8@QDs nanoprobe showed a selective accumulation of Cu²⁺ ions, which was developed for enhanced sensing of GST by the "off-on-off" strategy. As shown in Scheme 1, the fluorescence of ZIF-8@QDs could be quenched by Cu²⁺ through electron transfer and cation exchange processes. In the presence of GSH, the quenched fluorescence was recovered due to the strong affinity between Cu²⁺ and GSH. Under the catalysis of GST, the substrate of CDNB would have a conjugation reaction with GSH to form a product of CDNB-SG that could not coordinate with Cu²⁺, resulting in ZIF-8@QDs fluorescence quenching. Therefore, a highly red-emissive fluorescent sensing platform was successfully constructed for enhanced sensing of GST activity.