Noncovalently Stabilized Thermoresponsive Polymerization-Induced Electrostatic Self-Assembly

Nanostructured polyion complexes(PICs)have great potential applications in gene delivery,drug transport and so on.But the nanomorphologies of thermoresponsive PICs formed at higher temperature are difficult to be stable at lower temperature.In practical applications,such as for gene transfection,nanoreactors carriers and so on,the stabilization of PICs nanostructures is necessary.Generally,chemical crosslinking is often used to stabilize polyion complexes,but the process is complicated and produces biologically unfavourable chemicals.Recently,some researches have shown that the combination of electrostatic interaction and other interactions(hydrogen bonding,hydrophobic interaction,etc)can be used to realize noncovalent stabilization of PICs.But there are few studies in this area.Guanidinium group of arginine has both electrostatic interaction and multiple hydrogen bonding,which is called the salt-bridge interaction mode,to stabilize the complexes structures of proteins and nucleic acids.Therefore,the research about noncovalent stabilization of PICs using arginine derivatives is of great importance.Now most polyion complexes are assembled in dilute solution and it can not realize mass production.In recent years,the technology of polymerization-induced self-assembly(PISA)can prepare block copolymer nanoparticles under high concentration and have potential for mass production.Our research group is the first to employ polyion complexation in PISA and propose an approach of polymerization-induced electrostatic self-assembly(PIESA)for preparing well-defined PICs nanoparticles under high concentration.Based on the above understanding,we prepare a series of nanostructured thermoresponsive PICs with an arginine derivative that contains guanidinium groups(N-(2-guanidinoethyl)methacrylamide)(GEMA)using visible light-initiated PIESA.It can effectively stabilize the morphologies of PICs nanomaterials at room or lower temperature through heating-induced hydrogen bonding between the non-ionic hydrophilic blocks and PGEMA-based polyion complex components.Through the above research,We establish a new method of the thermoresponsive PIESA for preparing the noncovalently stabilized thermoresponsive polyion complex nanomaterials morphologiesFirstly,we use anionic poly(2-acrylamido-2-methylpropanesulfonic acid)(PAMPS100),non-ionic hydrophilic poly(N-2-hydroxypropylmethacrylamide)(PHPMA63)macro-chain transfer agent,sodium phenyl-2,4,6-trimethylbenzoylphosphinate(SPTP)initiator and cationic GEMA monomer to build a new PIESA system for synthesis of polyion complexes via visible light-initiated RAFT polymerization in aqueous solution at 25?.The degree of polymerization of PGEMA block(DPPGEMA)in the growing chain is 20,30,40,50,60,respectively.All the polymerizations are fully reactive and well-controlled,and the resultant polyion complexes are at isoelectric points.It is found that the morphologies change from monolayer colloidal nanosheets to nanowires with the increase of DPPGEMA.So it has significant chain length dependenceThen we dilute the synthesized PICs at 25? above into 1.0 mg/mL.The subunits within the colloidal nanosheets undergo a reversible sphere-cylinder transition when DPPGEMA is 20 and 30.This is because heating induces effective hydrogen bonding of the PHPMA hydrophilic blocks to PGEMA-based polyion complex components,which makes PHPMA dehydrated.The PHPMA block can be hydrated again when cooling.This demonstrates the reversible process.Thus,the polyion complexes with low DPPGEMA cannot fulfill noncovalent stabilization.We succeeds in noncovalent stabilization of the nano wires and vesicles when DPPGEMA is 60.The dehydrated PHPMA block cannot be hydrated again by cooling,which indicates an irreversible transformation.The formation of hydrogen bonding between the PHPMA hydrophilic blocks and the PGEMA-based polyion complex components participates in noncovalent stabilization of PICs,and the stabilization of the nanostructures is achieved by heating.The hydrogen bonding interaction is the interfacial interaction behavior,so these hydrogen bonds are not in the same plane.Thus,the synergy of hydrogen bonding and polyion complexation accounts for the noncovalent stabilization of PICs nanoparticles.Finally,by using a single formulation(DPPGEMA=60),a series of thermoresponsive PICs are synthesized in situ just by changing reaction temperatures.It suggests a sphere-nanowire-vesicle transformation when targeting higher temperatures.The PICs micelles,nanowires and vesicles synthesized at different temperatures are stable at 25?under dilute conditions.So we establish a new method of thermoresponsive PIESA for noncovalent stabilization of thermoresponsive polyion complex nanomaterials without complicated chemical crosslinking.In summary,we use cationic GEMA monomer to build a new polymerization-induced electrostatic self-assembly system to synthesize the thermoresponsive polyion complexes.When dilute the dispersions into 1.0 mg/mL,we succeed in noncovalent stabilization of the PICs micelles,nanowires and vesicles.This is because the PHPMA hydrophilic blocks form hydrogen bonding with the PGEMA-based polyion complex components.The PHPMA blocks dehydrate and participate in noncovalent stabilization of polyion complexes.Thus,the PICs nanoparticles achieved at higher temperature can stabilize at lower temperature.So we establish a new method of thermoresponsive polymerization-induced electrostatic self-assembly for noncovalent stabilization of thermoresponsive polyion complex nanomaterials without complicated chemical crosslinking.It enriches the stabilization approaches of PICs nanostructures and has great applications potential.