Thermoresponsive Dendronized Copolymers With Guanidine

In the practical applications,the delivery of drugs significantly limited by extracellular and intracellular biological barriers,which have led to the development of a large number of delivery systems that can overcome the barriers of various biological barriers.A special type of guanidine-containing cell-penetrating peptides and their analogues have been used as cells transporters for nucleic acids and proteins without causing significant membrane damage.Although it having excellent affinity with nucleic acids,the single function of such carriers severely limits its further applications.Oligoethylene glycol(OEG)-based dendronized polymers possess densely packed dendronized OEG pendant groups and show excellent temperature sensitivity,which afford them switchable encapsulation and shielding effect to the guest molecules.In this work,a series of guanidine-containing thermosensitive dendronized copolymers which can be used as smart drug delivery carriers were prepared.They show precise controlled release of nucleic acids,enzymatic degradation protection and cell transfection functions,which provide new opportunities to improve bioactivity and prolong bioavailability of drugs.The main contents include:(1)Through free radical copolymerization,a series of cationic OEG dendritic copolymers and their corresponding nanogels were prepared.They show characteristic temperature responsiveness,which can be regulated by changing the proportion of copolymer units.Moreover,their demonstrated outstanding biocompatibility and negligible cytotoxicity.(2)The binding and releasing capabilities of copolymer and nanogels to siRNA were investigated.It was found that these copolymers and nanogels had good loading capacity.The loading capacity of nanogels to si RNA is better than the corresponding copolymers,and enhances with the increase of nanogels particle size.In addition,these carriers can effectively release si RNA under the dual stimulation of temperature and ATP.(3)The protective properties of copolymers and nanogels to si RNA were investigated. It was found that nanogels exhibited better protection properties than those of copolymers under different p H,temperature and enzyme concentration conditions.(4)These cationic dendronized copolymers and their nanogels carriers could effectively transfect si RNA in vitro.In summary,we designed a series of copolymer and their corresponding nanogels with excellent binding ability to si RNA,remarkable protective ability to si RNA and effective transfection ability of si RNA.These new intelligent guanidine-based dendritic polymer carriers have broad application prospects in gene therapy fields.