Rapid and Versatile Construction of Polyphosphoester-based Nanostructures for Different Biological Applications

摘要

Engineered polymeric nanoparticles with unique physical and chemical properties at the nanoscale, emulating natural nanosystems (e.g., viruses, lipoproteins, and proteins) in both structural and functional features, have been bringing about a revolutionary impact on the pharmaceutical industry, due to their applications as diagnostic, therapeutic and theranostic agents for a wide variety of human diseases.1,2 Modern advances in polymerization methodologies and the application of reactive, efficient and orthogonal functionalization reactions, such as “click” chemistries, have enabled the engineering of functional block polymers to direct their self-assembly into nanoparticles with various sizes, surface charges and functionalities.3-7 However, it is still challenging to rapidly construct a biodegradable system that serves as a versatile platform, beginning from the point of small molecules and engineering them stagewise towards multifunctional nanoparticles with tunable properties. Recently, polyphosphoesters have been attracting considerable attention due to their potential for environmental and biological clearance, which allows for many applications, including in medical devices, for instance in tissue engineering, regenerative medicine, gene therapy, and controlled drug delivery.8,9 Compared with other synthetic degradable polymer systems, such as, polyesters, polycarbonates and polypeptides, polyphosphoesters had two advantageous structural features: highly water soluble backbone and easily functionalizable side-chain.10