Biocompatibility Studies Of Non-viral Gene Vector

Over the past two decades,the clinical application of gene-based therapy for treating or preventing a wide range of diseases has been investigated.However,success in clinical trials has been limited owing to numerous technical barriers.Association of drug delivery systems with blood proteins is considered the most critical step,determining to a major extent the nanoparticle biodistribution,efficacy and toxicity.In this study,we used micelle/precursor co-templating assembly?M/P-CA?strategy to fabricate unique molecularly organic–inorganic hybrid TB-MONs with radial large porous structure and?30 nm particle size and these particles are suitable for direct nuclear targeting.3-mercaptopropyltrimethoxysilane?MPTES?was introduced by post-synthesized and facilitate to functionalization.The growth of the CPD transporter on the TB-MONs in solution is initiated by a thiol that acts as an initiator of the disulfide-exchange polymerization.We studied the hemolysis of red blood cells and protein adsorption behavior of the sulfide bridging organic mesoporous silica nanoparticles and CPD modified nanoparticles.Results shows that with respect to the traditional MSNs,the protein adsorption and hemolysis percentage of TB-MONs were all decreased,and the introduction of CPD have little effect on protein adsorption and hemolytic effectsIn order to study the influence of structure on the interaction between nanoparticles and proteins,two typical polycations of equal molecular weight with different structures were used to study the interactions of them and their polyplexes with BSA,including graft copolymer named poly?N-vinylpyrrolidone?-g-poly?2-dimethylaminoethyl methacrylate??PVP-g-PDMAEMA,i.e.Pg P?and block copolymer named PVP-b-PDMAEMA?Pb P?.Fluorescence spectrum was used to confirm the binding affinities and binding ratios between polycations and BSA in static state.The binding constant of Pg P and BSA was 8.3×10⁴ M^-1,which was higherwas also confirmed by binding sites of Pb P and Pg P with BSA?0.3 vs 1.1?.Surface plasmon resonance sensor?SPR?was chosen to study the dynamical non-specific interaction between BSA and polycations as well as polyplexes.According to SPR results,the numbers of both Pb P and Pg P adsorbed on BSA increased with the concentration of polycations increasing,and the numbers of both Pb P and Pg P adsorbed on BSA increased with the N/P of polyplexes.