Targeted adhesion of dendrimer nanocarriers to hypoxia-injured primary cardiomyocyte cultures

Abstract

Objective To prepare nanocarriers capable of targeting hypoxia-injured cardiomyocytes and to investigate its physicochemical characteristics, cytotoxicity and efficiency of targeted binding to injured primary cardiomyocytes. Methods The dendrimer nanocarriers(non-targeting nanocarriers) and angiotensin Ⅱ Type 1(AT1)-modified dendrimer nanocarriers(targeting nanocarriers) were synthesized. The chemical structure, gene compact capacity, particle sizes and zeta potentials of the targeting nanocarriers were determined and the morphology was observed. The primary cardiomyocytes of neonatal SD rats were cultured in 3 different conditions: with non-targeting nanocarriers under hypoxia, with targeting nanocarriers under hypoxia, and with targeting nanocarriers under normal culture condition. The targeted adhesion of the nanocarriers to injured cardiomyocytes and normal cardiomyocytes were observed under a laser scanning confocal microscope and quantified with flow cytometry. The toxicity of nanocarriers to cardiomyocytes was also assessed. Results Non-targeting nanocarriers and targeting nanocarriers were successfully synthesized. When the weight ratio of targeting nanocarriers to gene was 6:1, the gene was completely incorporated, and formed spherical particles with a diameter of (180±55) nm and a zeta potential of +5.4 mV. When the concentrations of nanocarriers were less than 200 mg/L, the cell viability was more than 85% at a series of time points. Compared with hypoxia injury+non-targeted group and normal+targeted group, the targeted adhesion efficiency of myocardial cell membrane was significantly enhanced in hypoxia injury+targeted group. Conclusions AT1-modified dendrimer nanocarrier was successfully prepared, which can effectively bind to the injured cardiomyocytes overexpressing angiotensin Ⅱ type 1 receptors(AT1R) with low cytotoxicity. It may provide a new targeted delivery strategy for gene therapy of perioperative myocardial ischemia. Key words: Dendrimer; Cardiomyocyte; Targeting; Angiotensin Ⅱ type 1; Nanocarrier