Preparation And Properties Of Red Blood Cell-nanoparticle Composite Carriers

Nanoparticles have been widely used as drug carriers due to their excellent properties such as high designability,high drug loading efficiency and controllable release.Red blood cells(RBCs)are the most abundant blood cells in the human body.Their unique two concave disc structure and flexibility and mobility of the cell membrane endow them with the adaptive shape deformation property,which is excellent property for designing shear-responsive drug carrier.On the other hand,RBCs can avoid the capture of reticuloendothelial system and are able to cycle as long as 120 days in the body.Therefore,RBCs are very suitable for drug delivery carriers that have long circulation time.In nature,a variety of pathogens such as red cell body,barber worm parasite,can attach to the surface of the RBCs and escape from the immune system,and survive in the circulation system for a few weeks.Thus,if one can mimic such kind of behavior to construct RBCs-NPs composite carrier,the obtained carriers can make full use of the advantages of both nanoparticles and RBCs,including high drug-loading efficiency,drug targeting and long cycling time.What's more,we can construct shear-responsive drug carriers through the design of combined forces.But the mechanism of the interaction between nanoparticles and RBCs is not very clear.Thus it is difficult to effectively control the combination strength and shear response behavior.In this study,we first fabricated two kinds of model nanoparticles which can attach to two kinds of RBCs.The nanoparticles with different size,surface properties and structure were obtained.RBCs can be modified by polydopamine to change their surface properties.After simply mixing the RBCs and NPs together,RBC-NPs or PDA-RBCs-NPs composite carriers were constructed,and the influences of NPs' size,surface groups and charges on their adhesion behavior to RBCs were systematically studied.And then the shear-responsive behavior of composite carriers were also investigated using a microchannel device.The results show that the NPs can attach to the surface of RBCs by hydrophobic and electrostatic interaction,and can maintain the long cycling performance in the flow state.PDA-RBCs have better stability which is good for transportation and storage,and can be combined with BSA NPs through covalent interactions,which is more conducive to the realization of long circulating drug carriers.