Study On The Dynamic Stability Of Complex Coacervate Core Micelles

As functional soft nanocarriers,complex coacervate core micelles(C3Ms)haves been widely used in the field of biological diagnosis and treatment.Although the previous research has made a series of important progress in micellar preparation and application,the understanding of the dynamic properties of C3Ms is still limited.In particular,the understanding of the exchange of the polyions that compose the C3Ms with other surrounding molecules is crucial for evaluating their stability for safe application.In this paper,a series of experiments are designed to study the response and components exchange behavior of C3Ms when excessive components are introduced.Based on the pyridinedicarboxylic acid(DPA)based bisligand and their complexation wuth different metals,we prepared anionic coordination polymers with different structures,and further assembled with polycation-neutral block polymers to construct complex coacervate core micelles.Using different characterization methods such as laser light scattering,nuclear magnetic resonance,fluorescence and elemental analysis,we studied the stability of micelles and the substitution between different components when introducing excessive metal or DPA ligands.Our study has confirmed that excessive organic molecules are difficult to destroy complex coacervate core micelles,but excessive metal usually leads to the replacement of some metals in the micelles.The experimental results preliminarily revealed the dynamic stability of complex coacervate core micelles,which laid the foundation for the biological application of such materials.The specific research work is as follows:Firstly,the bis-ligand(LEO)of pyridine dicarboxylic acid was designed and synthesized.Upon coordinated with different metal ions,anionic coordination polymers with different structures are prepared,which assembly further with polyion-neutral diblock copolymers and form complex coacervate core micelles(C3Ms).Secondly,by adding excess DPA and LEO,it was found that the bis-ligand LEO is essential for the growth of coordination polymers and consequently the formation of micelles,leading to equilibrium structures with same micellar composition and structure independent on the order of mixing.DPA can neither participate in the formation of micelles nor affect the formed M-C3Ms.This indicates that the stronger binding component is easier to replace the weaker binding component.Hence,the designed M-C3Ms based on the strong binding components,as LEO-C3Ms,shall be relatively stable in biological surroundings,paving the way to the application of such particles as bio-imaging probes.Thirdly,by adding excess metal ions,it was found that the excess Zn2+can replace part of Ln3+from Ln-C3Ms,leading to a hybrid coordination structure with both Ln3+ and Zn2+.The released lanthanide ions may constitute a risk for bio-applications.However,the typical concentration of coordinating metal ions like Cu2+ or Zn2+ in biological fluids is so small that the risk is presumably negligible.Due to the excellent magnetic and fluorescent properties of lanthanide metals,we believe that Ln-C3Ms is expected to be used for in vivo biological applications.