Protease-triggered bioresponsive drug delivery for the targeted theranostics of malignancy

Proteases have a fundamental role in maintaining physiological homeostasis, but their dysregulation results in severe activity imbalance and pathological conditions, including cancer onset, progression, invasion, and metastasis. This striking importance plus superior biological recognition and catalytic performance of proteases, combining with the excellent physicochemical characteristics of nanomaterials, results in enzyme-activated nano-drug delivery systems (nanoDDS) that perform theranostic functions in highly specific response to the tumor phenotype stimulus. In the tutorial review, the key advances of protease-responsive nanoDDS in the specific diagnosis and targeted treatment for malignancies are emphatically classified according to the effector biomolecule types, on the premise of summarizing the structure and function of each protease. Subsequently, the incomplete matching and recognition between enzyme and substrate, structural design complexity, volume production, and toxicological issues related to the nanocomposites are highlighted to clarify the direction of efforts in nanotheranostics. This will facilitate the promotion of nanotechnology in the management of malignant tumors.

Dynamic effect of endothelin-converting enzyme on intimal hyperplasia after venous autograft / 中国普通外科杂志

Objective To study the effet of ET-1 and ECE on endothelial proliferation of autografted vein.Methods An animal model of the autogenous vein graft was established in 80 Wistar rats.The expression of ECE and EF-1 gene was determined by RT-PCR and immunohistological method to test the mRNA and protein expresion level respectively.Results PCNA positive smooth muscle cells appeared 6 hours after transplantation,increased with time,and reached a peak at 1 to 2 weeks.After 2 weeks,PCNA positive SMC in the tunica media began to decline and recovered to the 6 hour level at 8 weeks after the operation.mRNA of ECE increased with the time after the operation,reached a peak after 1-2 weeks,declined afterwards,and became stable at around 8 weeks.Expression change of ET1 was similar to the change of ECE,reached the peak after 1-2 weeks and was stable after 8 weeks(r=0.975).Conclusions The time and pattern of change of the pathologic process of intimal hyperplasia are in agreement with the expression of ET-1 and ECE,and suggests that ECE is involved in the process of intimal hyperplasia of vein graft.