Encapsulation of RNA by negatively charged human serum albumin via physical interactions

Human serum albumin (HSA) is the most abundant plasma protein and has an inherent ability to target tumor cells. It is an excellent candidate for drug delivery. However, HSA cannot form complex with DNA or RNA, because it is negatively charged under physiological conditions. In this work, we reported a simple method to prepare HSA/RNA nanoparticles mainly by physical interaction. Firstly, the solution pH is adjusted to 4.0, under which condition HSA is positively charged. It forms complex with RNA via electrostatic interaction. The solution is then heated at 75 oC for 15 min to stabilize the structure and the size of the formed complex. The HSA/RNA nanoparticle prepared by this method has a diameter about 110 nm and a narrow distribution. It is also stable for days under physiological conditions. Cellular essays demonstrate that these particles exhibit a high cellular uptake efficiency and non-toxicity to HeLa cells.