Deleterious effects to normal tissues and short biological half‐life of sonosensitizers limit the applications of sonodynamic therapy (SDT). Herein, a new sonosensitizer (Cu(II)NS) is synthesized that consists of porphyrins, chelated Cu2+, and poly(ethylene glycol) (PEG) to overcome the challenges of SDT. As Cu2+ contains 27 electrons, Cu(II)NS has an unpaired electron (open shell), resulting in a doublet ground state and little sonosensitivity. Overexpressed glutathione in the tumor can reduce Cu2+ to generate Cu(I)NS, leading to a singlet ground state and recuperative sonosensitivity. Additionally, PEG endows Cu(II)NS with increased blood biological half‐life and enhanced tumor accumulation, further increasing the effect of SDT. Through regulating the valence state of Cu, cancer SDT with enhanced therapeutic index is achieved.
H2S is a well-known toxic gas and also a gaseous signaling molecule involved in many biological processes. Advanced chemical tools that can regulate H2S levels in vivo are useful for...
Inflammatory bowel disease (IBD) affects millions of people each year. The overproduction of reactive oxygen species (ROS) plays a critical role in the progress of IBD and will be a potential therapeutic target. Here, we synthesize a kind of oral zero-valent-molybdenum nanodots (ZVMNs) for the treatment of IBD by scavenging ROS. These ultrasmall ZVMNs can successfully pass through the gastric acid and then be absorbed by the intestine. It has been verified that ZVMNs can down-regulate the quantity of ROS and reduce colitis in a mouse IBD model without distinct side effects. In addition, RNA sequencing reveals a further mechanism that the ZVMNs can protect colon tissues from oxidative stress by inhibiting the nuclear factor κB signaling pathway and reducing the production of excessive pro-inflammatory factors. Together, the ZVMNs will offer a promising alternative treatment option for patients suffering from IBD.
H2S is a gaseous signaling molecule that is involved
in many physiological and pathological processes. In general, the
level of intracellular H2S (<1 μM) is much lower
than that of GSH (∼1–10 mM), leading to the remaining
challenge of selective detection and differentiation of endogenous
H2S in live biosystems. To this end, we quantitatively
demonstrate that the thiolysis of NBD amine has much higher selectivity
for H2S over GSH than that of the reduction of aryl azide.
Subsequently, we developed the first NBD-based cell-trappable probe 1 (AM-BODIPY-NBD) for highly selective and ultrasensitive
imaging of intracellular H2S. Probe 1 demonstrates
a 207-fold fluorescence enhancement at 520 nm after reaction with
H2S/esterase to produce a bright BODIPY (quantum yield
0.42) and a detection limit of 15.7 nM. Probe 1 is water-soluble,
cell-trappable, and not cytotoxic. Based on this excellent chemical
tool, relative levels of basal H2S in different cell lines
were measured to reveal a positive correlation between endogenous
H2S and the metastatic potential of colon and breast cancer
cells. In addition, H2S biogenesis in vivo was also validated by probe 1 both in tobacco leaves
under viral infection and in zebrafish after tail amputation. It is
anticipated that probe 1 will have widespread applications
in imaging and for investigating different H2S-related
biological processes and diseases.
Dual-quenching fluorescent probes based on thiolysis of NBD thioether/ether/amine for fast and separate detection of H2S and Cys/Hcy in living cells were rationally constructed.
Near-infrared (NIR) fluorescent probes are attractive tools for bioimaging applications because of their low auto-fluorescence interference, minimal damage to living samples, and deep tissue penetration. H2S is a gaseous signaling molecule that is involved in redox homeostasis and numerous biological processes in vivo. To this end, we have developed a new red shifted fluorescent probe 1 to detect physiological H2S in live cells. The probe 1 is based on a rhodamine derivative as the red shifted fluorophore and the thiolysis of 7-nitro 1,2,3-benzoxadiazole (NBD) amine as the H2S receptor. The probe 1 displays fast fluorescent enhancement at 660 nm (about 10-fold turn-ons, k2 = 29.8 M−1s−1) after reacting with H2S in buffer (pH 7.4), and the fluorescence quantum yield of the activated red shifted product can reach 0.29. The probe 1 also exhibits high selectivity and sensitivity towards H2S. Moreover, 1 is cell-membrane-permeable and mitochondria-targeting, and can be used for imaging of endogenous H2S in living cells. We believe that this red shifted fluorescent probe can be a useful tool for studies of H2S biology.
A novel MT1-MMP activatable fluorogenic probe for tumor detection with enhanced specificity was developed via high-affinity and specific peptide conjugation.
It is difficult to develop highly selective substrate-based fluorescent nanoprobes for specific matrix metalloproteinases (MMPs) due to overlapping substrate specificities among the family of MMP enzymes. To resolve this issue, we have developed novel fluorescent nanoprobes that are highly selective for soluble MMP-2. Herein, MMP-2-responsive nanoprobes were prepared by immobilizing fluorescent fusion proteins on nickel ferrite nanoparticles via the His-tag nickel chelation mechanism. The fusion protein consisted of a fluorescent mCherry protein with a cell penetrating peptide (CPP) moiety. An MMP-2 cleavage site was also introduced within the fusion protein, which was directly linked to the nickel ferrite nanoparticles. The selectivity of nanoprobes was modulated by hiding the cleavage site of MMP-2 substrates deeply inside the system, which could result in strong steric hindrance between the nanoprobes and MMPs, especially for membrane-tethered MMPs such as MMP-14. A cell-based assay demonstrated that the nanoprobes could only be activated by tumor cells secreting soluble MMP-2, but not membrane-tethered MMP-14. To further evaluate the contribution of the steric hindrance effect on the nanoprobes, a truncated recombinant MMP-14 was employed to confer their cleavage activity as compared to native membrane-tethered MMP-14. Furthermore, a designed probe with a diminished steric hindrance effect was proved to be activated by membrane-tethered type MMP-14. The results indicated that the design of fluorescent nanoprobes employing the steric hindrance effect can greatly enhance the selectivity of MMP-responsive nanoprobes realizing the specific detection of soluble MMP-2 in a tumor microenvironment. We believe that highly selective MMP-2-responsive fluorescent nanoprobes have broad impacts on biomedical applications including molecular imaging and labeling for tumor detection.
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