Antilung cancer effect of ergosterol and cisplatin-loaded liposomes modified with cyclic arginine-glycine-aspartic acid and octa-arginine peptides.

Abstract

Lung cancer is one of the most important diseases threatening human health, and targeted therapy has become the main research direction. This work, therefore, aimed to develop cyclic arginine-glycine-aspartic (RGD) and octa-arginine (R8) peptide-modified ergosterol (ERG)-combined cisplatin (diamminedichloridoplatinum(II) [DDP]) liposomes (LIP) as a drug delivery system. Soybean phospholipids (SPC) and cholesterol (Chol) were selected to prepare different LIPs: ERG-loaded LIP (ERG-LIP), DDP and ERG-LIP (DDP/ERG-LIP), R8 peptide-modified DDP and ERG-LIP (R8-DDP/ERG-LIP), and cyclic RGD and R8-DDP/ERG-LIP (RGD/R8-DDP/ERG-LIP). The quality, tumor sphere penetrating ability, in vitro cellular uptake, mechanism of cellular uptake, and in vitro cytotoxicity of RGD/R8-DDP/ERG-LIP were evaluated. The LIP quality evaluation revealed that RGD/R8-DDP/ERG-LIP is round with a double-layer structure. The average particle size, dispersion coefficient of the polydispersity index (PDI), and zeta potential of RGD/R8-DDP/ERG-LIP were 155.2 ± 8.7 nm, 0.102, and 4.74 ± 0.7 mV, respectively. Furthermore, the LIPs were stable in the serum, and obviously inhibited the growth of A549 lung cancer cells with RGD/R8-DDP/ERG-LIP exhibiting the strongest inhibitory effect. The highest cellular uptake rate, which was at 4 hours, was exhibited by RGD/R8-DDP/ERG-LIP in a concentration-dependent manner. The results showed that LIP uptake by A549 cells was mainly by the clathrin-mediated endocytosis pathway (chlorpromazine). The results also suggest that RGD/R8-DDP/ERG-LIP might be a promising drug delivery system to improve antilung cancer drug effect and tumor-targeting in vitro.