白蛋白/透明质酸纳米颗粒制备及递送顺铂效果

Cisplatin (Cis) is one of the typical anti-tumor chemotherapeutic drugs, but its clinical application is restrained by severe toxic side effects and multidrug resistance. However, emerging nanotechnologies have great potential in overcoming the above problems. By means of the albumin templating method, an albumin/hyaluronic acid composite nanocarrier was prepared from albumin, hydrazided hyaluronic acid, and aldehyde hyaluronic acid. Cis could be loaded into the nanocarrier through Pt-hydrazide coordination chemistry. Fourier-transform infrared spectroscopy, proton nuclear magnetic resonance spectrum, transmission electron microscopy, and inductively coupled plasma mass spectrometry were employed to characterize the chemical structure of nanocarrier and the physiochemical properties of nanomedicine. The results showed that the nanomedicine exhibited a subsphaeroidal morphology with an average size of about 150 nm, and the loading content of Cis was as high as 10.8%. Moreover, the nanomedicine displayed a reduction/acid dual-responsive drug release behavior. In vitro cell experiments showed that the cytotoxicity of the nanocarrier was negligible, and the nanomedicine had good targeting ability towards hepatocellular carcinoma (HepG2) cells. Notably, the effect of nanomedicine in killing HepG2 cells was comparable to free cisplatin. Furthermore, it was found that inducing cell apoptosis was still a major mechanism of killing HepG2 cells by nanomedicine. The albumin/hyaluronic acid composite nanoparticle is a promising nanocarrier with excellent comprehensive performances for the targeting delivery of cisplatin with improved therapeutic efficacy and reduced toxic side effects in vivo .