Dual Functionalized Amino Poly (Glycerol Methacrylate) With Guanidine And Schiff-base Linked Imidazole For Gene Delivery

Nanocarriers with various compositions and biological properties have been extensively applied for in vitro/in vivo drug and gene delivery.The family of nanocarriers includes polymeric nanoparticles,lipid-based carriers,dendrimers,carbon nanotubes,and gold nanoparticles.Among different delivery systems,polymeric carriers have several properties,such as easy to synthesize,inexpensive,biocompatible,biodegradable,non-immunogenic,nontoxic,and water soluble.In addition,cationic polymers seem to produce more stable complexes,leading to a more protection during cellular trafficking than cationic lipids.Efficient transfection activity and minimal toxicity are crucial importance to development of gene delivery systems to practical applications.Over the past decade,polyglycerols and their structurally related analogs have received considerable attention in the biomedical field.In this work,poly(glycidyl methacrylate)(PGMA)was synthesized by atom transfer radical polymerization(ATRP),followed by introduction of cationic pedants ethanediamine(EDA)through ring-opening reaction,namely EP.Furthermore,EP was sequentially functionalization by strategic use of guanidine(GEP)and additional Schiff-base linked imidazole(IGEP).The structure of EP,GEP and IGEP were characterized by 1H NMR spectroscopy and FTIR spectroscopy.Molecular weights and polydispersity of polymers were assessed by gel permeation chromatography(GPC).The molar content of amino groups per gram of polymer was measured with an elemental analysis instrument.Next,we make three kinds of polymer complex with DNA,respectively,to build complex,and some properties of these complexes as gene carrier were tested.Subsequent investigations revealed the PGMA derivative capable of sufficiently binding to plasmid DNA(pDNA)and formulating optimal sized 100 nm nanoparticle with positive ζ potentials of 10-30 mV.The morphology of nanoparticles was characterized using scanning electron microscope.Biological evaluations demonstrated strategic use of guanidine resulting in enhanced cellular uptake and nuclear localization activities by virtue of its favorable affinity to the cellular membrane,and Schiff-base linked imidazole resulting in promoted endosome escape and DNA cargo releasing behaviors,consequently leading to efficient transfection in the targeted cells.Another noteworthy was guanidine and imidazole for minimized cytotoxicity,hence,these advantageous features provided substantial information to construct safe and efficient gene delivery carrier towards practical development.