Development of "smart" noninvasive bioimaging probes for trapping specific enzyme activities is highly desirable for cancer therapy in vivo. Given that β-galactosidase (β-gal) is an important biomarker for cell senescence and primary ovarian cancers, we design an enzyme-activatable ratiometric near-infrared (NIR) probe (DCM-βgal) for the real-time fluorescent quantification and trapping of β-gal activity in vivo and in situ. DCM-βgal manifests significantly ratiometric and turn-on NIR fluorescent signals simultaneously in response to β-gal concentration, which makes it favorable for monitoring dynamic β-gal activity in vivo with self-calibration in fluorescent mode. We exemplify DCM-βgal for the ratiometric tracking of endogenously overexpressed β-gal distribution in living 293T cells via the lacZ gene transfection method and OVCAR-3 cells, and further realize real-time in vivo bioimaging of β-gal activity in colorectal tumor-bearing nude mice. Advantages of our system include light-up ratiometric NIR fluorescence with large Stokes shift, high photostability, and pH independency under the physiological range, allowing for the in vivo real-time evaluation of β-gal activity at the tumor site with high-resolution three-dimensional bioimaging for the first time. Our work provides a potential tool for in vivo real-time tracking enzyme activity in preclinical applications.

The rational design of high-performance fluorescent materials for cancer targeting in vivo is still challenging. A unique molecular design strategy is presented that involves tailoring aggregation-induced emission (AIE)-active organic molecules to realize preferable far-red and NIR fluorescence, well-controlled morphology (from rod-like to spherical), and also tumor-targeted bioimaging. The shape-tailored organic quinoline-malononitrile (QM) nanoprobes are biocompatible and highly desirable for cell-tracking applications. Impressively, the spherical shape of QM-5 nanoaggregates exhibits excellent tumor-targeted bioimaging performance after intravenously injection into mice, but not the rod-like aggregates of QM-2.

H2S produced in small amounts by mammalian cells has been identified in mediating biological signaling functions. However, the in situ trapping of endogenous H2S generation is still handicapped by a lack of straightforward methods with high selectivity and fast response. Here, we encapsulate a semi-cyanine-BODIPY hybrid dye (BODInD-Cl) and its complementary energy donor (BODIPY1) into the hydrophobic interior of an amphiphilic copolymer (mPEG-DSPE), especially for building up a ratiometric fluorescent H2S nanoprobe with extraordinarily fast response. A remarkable red-shift in the absorption band with a gap of 200 nm in the H2S response can efficiently switch off the Förster resonance energy transfer (FRET) from BODIPY1 to BODInD-Cl, subsequently recovering the donor fluorescence. Impressively, both the interior hydrophobicity of supramolecular micelles and electron-withdrawing nature of indolium unit in BODInD-Cl can sharply increase aromatic nucleophilic substitution with H2S. The ratiometric strategy based on the unique self-assembled micellar aggregate NanoBODIPY achieves an extremely fast response, enabling in situ imaging of endogenous H2S production and mapping its physiological and pathological consequences. Moreover, the amphiphilic copolymer renders the micellar assembly biocompatible and soluble in aqueous solution. The established FRET-switchable macromolecular envelope around BODInD-Cl and BODIPY1 enables cellular uptake, and makes a breakthrough in the trapping of endogenous H2S generation within raw264.7 macrophages upon stimulation with fluvastatin. This study manifests that cystathione γ-lyase (CSE) upregulation contributes to endogenous H2S generation in fluvastatin-stimulated macrophages, along with a correlation between CSE/H2S and activating Akt signaling pathway.

Paclitaxel (PTX) is an extensively used potent chemotherapy drug; however, low water solubility, poor bioavailability, and emergence of drug resistance in patients limited its biological application. In this report, we proposed a new drug delivery system for cancer therapy based on graphene oxide (GO), a novel 2D nanomaterial obtained from the oxidation of natural graphite, to improve the utilization rate of PTX. PTX was first connected to biocompatible 6-armed poly(ethylene glycol), followed by covalent introduction into the surface of GO sheets via a facile amidation process under mild conditions, affording the drug delivery system, GO-PEG-PTX (size 50-200 nm). GO-PEG nanosized carrier could quickly enter into human lung cancer A549 and human breast cancer MCF-7 cells verified by inverted fluorescence microscope using fluorescein isothiocyanate as probe. This nanocarrier was nontoxic to A549 and MCF-7 cells without linking with PTX. Nevertheless, GO-PEG-PTX showed remarkably high cytotoxicity to A549 and MCF-7 cells in a broad range of concentration of PTX and time compared to free PTX. This kind of nanoscale drug delivery system based on PEGylated GO may find widespread application in biomedicine.

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