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1.
Chem Sci ; 12(1): 239-246, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34163592

RESUMO

Heparanase (HPA) is a critical enzyme involved in the remodeling of the extracellular matrix (ECM), and its elevated expression has been linked with diseases such as various types of cancer and inflammation. The detection of heparanase enzymatic activity holds tremendous value in the study of the cellular microenvironment, and search of molecular therapeutics targeting heparanase, however, no structurally defined probes are available for the detection of heparanase activity. Here we present the development of the first ultrasensitive fluorogenic small-molecule probe for heparanase enzymatic activity via tuning the electronic effect of the substrate. The probe exhibits a 756-fold fluorescence turn-on response in the presence of human heparanase, allowing one-step detection of heparanase activity in real-time with a picomolar detection limit. The high sensitivity and robustness of the probe are exemplified in a high-throughput screening assay for heparanase inhibitors.

2.
Sci Rep ; 9(1): 2102, 2019 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-30765819

RESUMO

Detection of cellular senescence is important not only in the study of senescence in various biological systems, but also in various practical applications such as image-guided surgical removal of senescent cells, as well as the monitoring of drug-responsiveness during cancer therapies. Due to the lack of suitable imaging probes for senescence detection, particularly in living subjects, we have developed an activatable near-infrared (NIR) molecular probe with far-red excitation, NIR emission, and high "turn-on" ratio upon senescence-associated ß-galactosidase (SABG) activation. We present here the first successful demonstration of NIR imaging of DNA damage-induced senescence both in vitro and in human tumor xenograft models.


Assuntos
Senescência Celular , Neoplasias do Colo/patologia , Dano ao DNA , Processamento de Imagem Assistida por Computador/métodos , Microscopia de Fluorescência/métodos , Animais , Apoptose , Proliferação de Células , Neoplasias do Colo/genética , Feminino , Corantes Fluorescentes , Humanos , Camundongos , Camundongos Nus , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
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