Salecan is a novel water-soluble extracellular b-glucan produced by a salt-tolerant strain Agrobacterium sp.ZX09. Salecan is suitable for the fabrication of hydrogels for biomedical applications due to its excellent physicochemical and biological properties. In this paper, a series of pH-sensitive hydrogels were prepared in aqueous solution by the graft copolymerization of Salecan and acrylic acid (AA) using N,N 0 -methylene diacrylamide as a crosslinker for controlled drug delivery. The structure and thermal stability of the resulting hydrogels were characterized by FT-IR, XRD and TGA. By SEM analysis, freeze-dried hydrogels displayed an interconnected porous structure with tunable pore size in the range of 23.2-90.3 mm. The swelling behavior of the hydrogels was shown to be highly dependent on the environmental pH, salt type and concentration, as well as the contents of Salecan and BAAm. They are almost unswellable at pH 1.2 and swollen extensively at pH 6.86. Meanwhile, the increase in the content of hydrophilic Salecan could enhance the swelling ratio, whereas the presence of more BAAm reduced the swelling capacity but promoted the water retention to some extent. Rheological tests revealed that storage modulus G 0 was strongly influenced by the crosslink density of the obtained hydrogel network.Especially, doxorubicin (DOX) as a model anti-cancer drug was very efficiently loaded into the negatively charged hydrogels (up to 69.4 wt%) through electrostatic interactions. More importantly, the release of DOX from this intelligent system exhibited pH-responsive behavior and a sustained release pattern. For SPA2, the cumulative release profile showed a low level of drug release (about 12.3 wt% in 24 h) at pH 7.4, and was significantly accelerated at pH 4.0 (over 40 wt% in 6 h). Cytotoxicity experiments confirmed that all blank hydrogels were non-toxic to A549 cells, while DOX released from the drug-loaded hydrogels remained biologically active and had the capability to kill cancer cells. The preliminary results clearly suggested that the Salecan-g-PAA hydrogels may be promising carriers for controlled drug delivery.

Activatable multimodal probes that show enhancement of multiplex imaging signals upon interaction with their specific molecular target have become powerful tools for rapid and precise imaging of biological processes. Herein, we report a stimuli-responsive disassembly approach to construct a redox-activatable fluorescence/F-MRS/H-MRI triple-functional probe 1. The small molecule probe 1 itself has a high propensity to self-assemble into nanoparticles with quenched fluorescence, attenuated F-MRS signal, and highH-MRI contrast. Biothiols that are abundant in reducing biological environment were able to cleave the disulfide bond in probe 1 to induce disassembly of the nanoparticles and lead to fluorescence activation (∼70-fold), F-MRS signal amplification (∼30-fold) and significant r relaxivity reduction (∼68% at 0.5 T). Molecular imaging of reducing environment in live cells and in vivo was realized using probe 1. This approach could facilitate the development of other stimuli-responsive trimodal probes for molecular imaging.

Cathepsin B (CTB) is a lysosomal protease which has been recognized as a promising biomarker for many malignant tumors, and accurate detection of its activity is important in early diagnosis of cancers and predicting metastasis. Herein, we reported a lysosome-targeting fluorogenic small-molecule probe for fluorescence imaging of lysosomal CTB in living cancer cells by incorporating a CTB-recognitive peptide substrate Cbz-Lys-Lys-p-aminobenzyl alcohol (Cbz-Lys-Lys-PABA) and a lysosome locating group morpholine. We demonstrated that the probe could be efficiently activated by CTB to generate ∼73-fold enhancement in fluorescence under acidic lysosomal environment (pH 4.5-6.0), allowing for high sensitivity and specificity to detect CTB. Fluorescence imaging results showed selective accumulation and fluorescence turn-on in the lysosomes of cancer cells, which were capable of reporting on lysosomal CTB activity in cancer cells and normal tissue cells. This study highlights the potential of using a lysosome-targeting group to design a sensitive and specific fluorogenic probe for fluorescence imaging of lysosomal CTB in living cells.

γ-Glutamyl transpeptidase (GGT) is a cell-membrane-bound enzyme that is involved in various physiological and pathological processes and is regarded as a potential biomarker for many malignant tumors, precise detection of which is useful for early cancer diagnosis. Herein, a new GGT-activatable near-infrared (NIR) fluorescence imaging probe (GANP) by linking of a GGT-recognitive substrate γ-glutamate (γ-Glu) and a NIR merocyanine fluorophore (mCy-Cl) with a self-immolative linker p-aminobenzyl alcohol (PABA) is reported. GANP was stable under physiological conditions, but could be efficiently activated by GGT to generate ≈100-fold enhanced fluorescence, enabling high sensitivity (detection limit of ≈3.6 mU L ) and specificity for the real-time imaging of GGT activity as well as rapid evaluation of the inhibition efficacy of GGT inhibitors in living tumor cells. Notably, the deep tissue penetration ability of NIR fluorescence could further allow GANP to image GGT in frozen tumor tissue slices with large penetration depth (>100 μm) and in xenograft tumors in living mice. This GGT activatable NIR fluorescence imaging probe could facilitate the study and diagnosis of other GGT-correlated diseases in vivo.

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