| Nonlinear amphiphiles have various topological structures,such as star,dendrimer,cycle,brush and three-dimensional network shapes.Molecular topological structures have an important effect on their physico-chemical properties and self-assembly.Because of the influence of topological structures,nonlinear amphiphiles are showing enormous advantages in the field of biomedical applications.Although experiment studies have proved that nonlinear amphiphiles have different self-assembly structures,thermodynamic properties and crystallization compared with linear counterparts.However,there are some key scientific questions remaining unclear,for example,the relationship between the nonlinear topological structures and the self-assembly behavior and mesoscopic structures of molecular aggregates;the influencing mechanism of mesoscopic structures of molecular aggregates on the structural stability,drug encapsulation and controlled release and endocytosis pathway of drug carrier s.From the perspective of mesoscopic structures,making clear these key scientific questions have a significant effect on the regulation of self-assembly structures and the optimization of application performances.In the view of simulation methods,we used the synergistic control method of crosslinking and electrostatic interaction,the rigidity control method of polymer chain,endocytosis model and fluid shear model,providing the technical support for the simulation research on the regulation of mesoscopic structures and applications of nonlinear polymers.In content,based on the key idea of “microscale-mesoscale-macroscale” and the design theory of chemical products,we adopted DPD simulation method to construct the coarse-grained models of amphiphiles with different topological structures,including the star,dendrimer,cycle,brush and three-dimensional network shapes.We further studied the topological effect of selfassembly behavior of amphiphilic molecules,revealed the influencing mechanism of topological structures on the mesoscopic structures of self-assembled aggregates,and established the structure-property relationship between the mesoscopic structures and the structural stability,drug encapsulation and controlled release,and endocytosis pathway of drug carrier s.Based on the complex synthesis and lack of responsiveness of anisotropic structures with phase-separated surface patterns,we constructed the the coarse-grained models of small amphiphiles,dirhamnolipid(di RL),and adopted DPD method to observe the pH-responsive surface pattern of micelles from a single type of lipid.Further study focused on the influence factors of phase-separated surface pattern,such as molecular structure,solvent selectivity and intramolecular interaction.As pH increased from 4.0 to 7.4,the surface pattern of micelles could transform from uniform surface to phase-separated surface,self-assembling into various complex anisotropic structures,such as patchy spherical micelles,rod-like micelles with helical surface pattern and a lamellar phase with a phase-separated surface pattern.The change in surface pattern resulted from the diverse molecular arrangement in the course of assembly due to the deprotonation of carboxyl groups.The influence factors,such as molecular structure,solvent selectivity and intramolecular interaction,could promote the formation of phaseseparated surface pattern and regulate the topological structures of micellar surfaces.Although the drug carrier of unimolecular micelles has excellent micellar stability,there are some inherent shortcomings for unimolecular micelles: poor drug loading and release capabilities.How to remain the excellent micellar stability under the condition of short hydrophilic chains may be a key point to balance the micellar stability and drug encapsulation and release.Therefore,we constructed the coarse-grained models of amphiphilic polymer molecules with various topological structures comprising poly(ethylene oxide)(PEO)as the hydrophilic block,poly(N,N-diethylamino-2-ethyl methacrylate)(PDEAEMA)as the pHresponsive block and polymethyl methacrylate(PMMA)as the hydrophobic block.We adopted a DPD method to investigate the synergetic effect of crosslinking and electrostatic repulsion on stability of unimolecular micelles.The well-performed stability of unimolecular micelles was endowed with various supramolecular polymer with short hydrophilic chains through the synergistic effect of crosslinking and electrostatic repulsion.The synergetic mechanism of crosslinking and electrostatic repulsion on the stability of unimolecular micelles was illustrated in terms of the microstructural transformation and mixing energy.The shrinkage degree of hydrophobic cores mattered to the stability of unimolecular micelles.The crosslinked and protonated DEAHEMA blocks maximized the extension degree of hydrophilic blocks(EO beads)due to the increasing steric hindrance and poor compatibility between DEAHEMA and EO blocks.The increasing extension degree of hydrophilic blocks could enhance the protective ability for hydrophobic cores,resulting in the maximum degree of core shrinkage.Therefore,even at the conditions of short hydrophilic chains and high polymer concentrations,monlinear polymers still had extremely high stability of unimolecular micelles.Cyclic backbones may endow cyclic polymers with distinctive self-assembly behaviors and functions.We systematically conducted a comparative study between cyclic grafted copolymers with rigid and flexible rings in the self-assembly behavior,and further proposed the energy-driven assembly mechanism of rigid rings.Under the condition of high hydrophilicity and small ring size,cyclic grafted copolymers with rigid rings tended to self-assemble into unimolecular micelles.With the increasing ring size,they could transform into spherical multimolecular micelles in a channel-type stacking way of rigid rings.However,as the hydrophilicity of polymers decreases,large-size rigid rings presented a novel channel-layercombination layout,and thus rigid copolymers self-assembled into ellipsoidal micelles.The channel-layer-combination arrangements of rigid rings could be showcased as a favorable equilibrium structure,which was determined by the balance between Emicelle and Eint.We have further regulated a series of complex self-assembling structures by adjusting the ring size,grafting density and mass concentration.Compared with flexible counterparts,the microstructural characteristics endowed the advantages of cyclic grafted copolymers with rigid rings in biomedical applications of the drug encapsulation,controlled release and endocytosis.Directed self-assembly(DSA)has been proved to be a promising strategy to control spatial structures of nanomaterials from microscopic to macroscopic length scale,showing attractive applications in microelectronics,energy materials and biomaterials.We proposed a simple and versatile strategy to construct various anisotropic nanostructures through the directed selfassembly(DSA)of patchy microgels.Patchy microgels could undergo directional arrangement process in the way of adsorption,translation and rotation,and self-organized into 1D nanorods in one direction at different concentrations.Patchy microgels needed to possess the strongly hydrophobic core,the extremely hydrophilic and charged shell,large hydrophobicity difference between core and shell to fulfill the DSA behavior,where the hydrophilicity of microgel shell was the most predominated influencing factor in DSA strategy.Patchy microgels with different number of patches could also directionally self-assemble along multiple directions into more complex anisotropic polymorphs,such as the novel 2D or 3D structures of V/T/h/cross shapes,multiple arms,multidirectional bending,single ring,multiple rings and nanocages.Moreover,microgel assemblies possessed high shear stability.The above results could be useful for the design and optimization of the molecular structure of polymers and micellar mesostructure,providing the design ideas and theoretical support for versatile drug delivery systems systematicallly. |
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