Construction of siNLRP3-loaded ultrasound response nanosystem and its therapeutic effect on diabetic cardiomyopathy / 西安交通大学学报(医学版)

ABSTRACT

【Objective】 To evaluate the protective effect of siNLRP3-loaded nanosystem on diabetic cardiomyopathy (DCM) via silencing NLRP3 under ultrasound-targeted microbubble blasting (UTMD). 【Methods】 After synthesis of polyethylene glycol polylysine block copolymer (mPEG-b-PLLys), siNLRP3-loaded hetero-assembled nanosystem system (siNLRP3-NBs) was constructed and characterized. Subsequently, a DCM rat model was established to investigate the protective effect of siNLRP3-NBS on the heart. Cardiac function of the rats was observed by small animal ultrasonography. HE and Masson staining were used to observe the degree of myocardial fibrosis change; the protein expression of NLRP3 and cell pyroptosis indexes were detected by Western blotting. 【Results】 1H NMR indicated that the structure of mPEG-b-PLLys was correct. The results of agarose electrophoresis showed that NBs could protect naked siNLRP3 from RNAase degradation, and the particle size and zeta potential of siNLRP3-NBs were (379.7±14.8) nm and (8.73±1.93) mV, respectively. The shape of NBs was almost spherical. siNLRP3-NBs combined with UTMD could enhance the protective effect on cardiac function and improve myocardial fibrosis in DCM rats. Protein expression indicated that UTMD could enhance the inhibitory effect of siNLRP3-NBS on cardiomyocyte pyroptosis. 【Conclusion】 UTMD-mediated ultrasonic response combined nanosystem can enhance the therapeutic effect of siNLRP3 on DCM, suggesting that ultrasonic response siNLRP3-loaded nanosystem is a potentially effective strategy for the treatment of heart disease.