PCSK9 Targeted Autophagosome-Tethering Compounds: Design, Synthesis, and Antiatherosclerosis Evaluation.

Atherosclerosis is a multifaceted disease involving various cell types and complex mechanisms, and it is the main cause of cardiovascular disease. Proprotein convertase subtilisin/kexin type-9 (PCSK9) has been identified as an effective target for treating atherosclerosis; however, most current research focuses on biological drugs. Our work optimized the previously reported autophagosome-tethering compound , and specifically, compound induced PCSK9 degradation with a 5-fold increase in activity and a 6-fold increase in bioavailability.

Targeted Degradation of PCSK9 In Vivo by Autophagy-Tethering Compounds.

Proprotein convertase subtilisin/kexin type-9 (PCSK9), a secreted protein that is synthesized and spontaneously cleaved in the endoplasmic reticulum, has become a hot lipid-lowering target chased by pharmaceutical companies in recent years. Autophagosome-tethering compounds (ATTECs) represent a new strategy to degrade targeted biomolecules. Here, we designed and synthesized PCSK9·ATTECs that are capable of lowering PCSK9 levels via autophagy in vivo, providing the first report of the degradation of a secreted protein by ATTECs.

A water-soluble fluorescent probe for real-time visualization of γ-glutamyl transpeptidase activity in living cells.

γ-glutamyl transpeptidase (GGT) is a kind of cell-surface enzyme that is overexpressed in many cancer cells. It is of great significance to develop an ideal tool for the diagnosis of GGT-rich cancer cells. Here, we reported a simple-structured but effective imaging probe for the detection of GGT activity.

An activatable fluorescent probe for imaging endogenous nitric oxide via the eNOS enzymatic pathway.

Nitric oxide (NO) is an essential cellular messenger molecule involved in various physiological and pathological processes. Thus, monitoring the dynamic presence of endogenous NO in living cells is of great significance. In this paper, we developed an activatable fluorescent nanoprobe BOD-NH-NP for endogenous NO detection.

Real-Time Monitoring Renal Impairment Due to Drug-Induced AKI and Diabetes-Caused CKD Using an NAG-Activatable NIR-II Nanoprobe.

Real-time in vivo optical imaging of kidney function is important for the diagnosis of renal diseases, such as acute kidney injury (AKI) and chronic kidney disease (CKD), with high morbidity and mortality worldwide. However, the reported optical imaging agents still have limitations for identifying AKI or CKD in the early stage due to their low sensitivity, poor tissue penetration, and significant background interference. Herein, an -acetyl-β-d-glucosaminidase (NAG)-activatable second near-infrared (NIR-II) fluorescent nanoprobe (BOD-II-NAG-NP) is developed for monitoring the progression of drug-induced AKI and in vivo imaging of diabetes-caused CKD.

Imaging of Senescent Vascular Cells in Atherosclerotic Mice Using a β-Galactosidase-Activatable Nanoprobe.

Senescence-associated diseases have severely diminished the quality of life and health of patients. However, a sensitive assay of these diseases remains limited due to a lack of straightforward methods. Considering that senescence-associated β-galactosidase (SA-β-Gal) is overexpressed in senescent cells, the detection of SA-β-Gal in senescent cells and tissues might be a feasible strategy for the early diagnosis of SA diseases.

Imaging of ovarian cancers using enzyme activatable probes with second near-infrared window emission.

We herein develop two β-galactosidase (β-Gal) activatable NIR fluorescent probes for visualizing ovarian cancers. Particularly, probe BOD-M-βGal produced NIR-II emission light at 900-1300 nm upon β-Gal activation. By using our activatable and target specific NIR-II probe for deep-tissue imaging of β-Gal overexpressed ovarian cancer cells, rapid and accurate imaging of ovarian tumors in nude mice was achieved.