With increasing knowledge of the molecular mechanisms of endogenous RNA interference,systemic delivery of small interfering RNA（siRNA） via targeted nanoparticles has emerged as a potential strategy for cancer gene therapy.In this study,a novel formulation[liposome-protamine-chondroitin sulfate nanoparticles（LPC-NP）]was developed for siRNA delivery by self-assembling with charge-charge interaction.The LPC-NP was further modified by DSPE-PEG_（2000） and DSPE-PEG_（2000）-T7 by the post-insertion method.T7,a transferrin-like seven-amino acid peptide,is a targeting ligand for transferrin receptor-overexpressed MCF-7 breast cancer cells.The particle size and zeta potential of LPC-NP were approximately 90 nm and ＋35 mV,respectively. It was shown that PEG modification could significantly decrease aggregation of LPC-NP in serum,and T7 peptide modified LPC-NP could significantly increase the cellular uptake and the gene-silencing effect of siRNA.In vitro cytotoxicity assay exhibited that significant cell growth inhibition was achieved in MCF-7 cells after the delivery of anti-EGFR siRNA.Our encouraging results suggested that T7-modified LPC-NP might be a promising carrier for RNAi-based tumor therapy.
A general method was described to synthesize a highly hydrophobic cyclic peptide,cyclo[LWLWLWLWLQ]where underlines indicate D-configuration of the amino acid,by a two-step solid-phase/solution synthesis strategy.The linear decapeptide was assembled by standard Boc chemistry on solid-phase and subsequently cyclized in solution with high efficiency and reproducibility. In subsequent purification by semi-preparative HPLC,50%(v/v) DMF/H_2O was employed as the solvent to overcome the difficulty of solubilization...
Docetaxel （DTX） was incorporated into albumin nanoparticles to form the docetaxel loaded nanoparticles （DTX-NPs） with a high-pressure homogenization method. The purpose of this procedure was to improve the solubility, stability and biocompatibility of DTX. In our study, particle size, zeta potential, size distribution, and encapsulation efficiency were investigated. The crystalloid state of DTX in nanoparticles was further determined by the X-ray diffraction technique. The hemolysis rate, pharmacokinetics and pharmacodynamics of the DTX-NPs were analyzed and compared with the injectable docetaxel solution （DTX-Sol）, which was fabricated according to the formulation of the commercial Taxotere. It demonstrated that the DTX-NPs were prepared successfully with these properties, including the （193±4） nm size, （-30±1） mV zeta potential and 69%±2% encapsulation efficiency. Higher stability was achieved in the lyophilized nanoparticles compared to that in the nanoparticle suspension. Furthermore, less hemolysis effect was observed in the DTX-NPs than that in the DTX-Sol. The pharmacokinetic and pharmacodynamic behaviors of the DTX-NPs were similar as that of DTX-Sol based on the in vivo experiments. In conclusion, albumin nanoparticles may act as a useful and safe carder for DTX.
