mulation in tumor tissue through the EPR effect and quickly releasing Cy5-siRNA in intracellular acidic conditions (Scheme [1](#F8){ref-type="fig"}). The higher accumulation of nanoparticles in the lung may have been a result of the aggregates lodging in fenestrated capillaries. Some particles may have adsorbed to different types or amounts of serum proteins and became entrapped in the capillary bed of the lung \[[@R44]--[@R47]\]. The fluorescence signal was weaker in the liver because most of the nanoparticles were not captured by the mononuclear phagocyte system (MPS) and the reticuloendothelial system (RES) in the liver.

![NP~mPEG-PE/CaP~ for the systemic delivery of siRNA and cellular uptake.](oncotarget-07-2855-g008){#F8}

CaP is considered the most biocompatible inorganic biomaterial and is a suitable candidate drug carriers as it is the main mineral found in human bone and teeth \[[@R48], [@R49]\]. Moreover, natural cephalin is a major component of cell membranes and is considered an excellent biocompatibile biomaterial. The biocompatibility of hybrid nanopariticles was studied by testing haemolytic activity, cytotoxicity and systemic toxicity. The results of this study demonstrated that the haemolysis percentage of NP~mPEG-PE/CaP~ at the highest concentration of 1000 μg/mL was still low (12%) due to the mPEG on the surface of NP~mPEG-PE/CaP~. The nanoparticles possessed a negligible cytotoxicity even at hybrid nanoparticles concentrations of 2000 μg/mL. In addition, the intravenous injection of nanoparticles induced no obvious toxicity under the experimental conditions. Overall, mPEG-PE and CaP hybrid nanoparticles are suitable candidates for drug carriers due to their excellent biocompatibility.

In conclusion, an amphiphilic mPEG-PE copolymer was synthesized by conjugating PE with mPEG-COOH. We have developed a hybrid nanocarrier system consisting of CaP and an mPEG-PE copolymer for safe and efficient siRNA delivery. It was demonstrated that mPEG-PE/CaP nanoparticles showed stable properties, good bi