Preparation And Imaging Study Of PH-responsive Polymer Micelles

As new drug delivery carriers,polymeric micelles have been widely used in the diagnosis and treatment of cancer over the past two decades.With the in-depth study of micelles,a series of intelligent responsible(pH,temperature,redox,light,magnetic field,ionic strength)polymer micelles have emerged and have been recognized by clinic.In addition,polymer-based nanobiosensors have attracted a lot of attention in the application of biological imaging due to their high sensitivity and biocompatibility.In this paper,we designed and prepared a series of pH-responsive fluorescent polymic micelles by combining a monomer with pH sensitivity and a monomer with fluorescence.Subsequently,we combined them with the magnetic nanoparticles to obtain the dual-modality optical imaging probes with tracer function,and the in vitro cytotoxicity and drug controlled release behavior were studied.The main work is as follows:Firstly,a pH-responsive fluorescent MPEG1000-PU multi-block polymer was successfully prepared by polycondensation using 1,4-bis(hydroxyethyl)piperazine(HEP)as the pH-responsive segment.The resulting polymer could self-assemble into a core-shell micellar structure.The particle size and fluorescence of MPEG1000-PU polymer micelles exhibited a strong pH sensitivity.Moreover,the results of MTT assay showed that the resulting MPEG1000-PU multi-block polymer had a low toxicity.In addition,due to the introduction of side chain of carboxyl functional groups,polymer micelles could be introduced into targeting ligands or encapsulate guest molecules by covalent and/or electrostatic interactions.Then,based on the first part of the work,a series of pH-responsive charge reversible fluorescent MPEG5000-PU was prepared by stepwise polymerization,in which 1,4-bis(hydroxyethyl)piperazine(HEP)and sulfamethazine(SM)as pH-sensitive molecules and fluorescein isothiocyanate(FITC)as a chromophore.The resulting polymer micelle has a smaller size(less than 200 nm)and could be stable for two weeks.At the same time,the charge of the MPEG5000-PU polymer exhibited a good pH-responsibility,and the charge and fluorescence of the polymer changed significantly with the change of pH.MTT assay showed that MPEG5000-PU polymer micelles had lower cytotoxicity and good biocompatibility.Besides,the polymer micelles exhibited a significant pH responsiveness to DOX in vitro release behavior.Finally,based on the above work,a series of pH-responsive dual-mode imaging polymer micelles were prepared as potential optical imaging probes by introducing the magnetic iron oxide nanoparticles(Fe3O4)into the system.Combining with fluorescein isothiocyanate(FITC),the polymer micelle could achieve the combination magnetic resonance(MRI)and optical imaging.The resulting pH-responsive polymer could self-assemble into a core-shell spherical structure at physiological pH value.Therefore,Fe3O4 nanoparticles could be well encapsulated in the hydrophobic core of the micelles by hydrophobic interaction.In addition,the morphology and thermal stability of polymer micelles of Fe3O4 nanoparticles and Fe3O4 nanoparticles were tested by transmission electron microscopy(TEM)and thermogravimetric analysis(TGA),respectively.Subsequently,the cytotoxicity was assessed by MTT assay,and the results showed that the polyurethane micelle had a low cytotoxicity,thereby,it was expected to be applied as a smart optical imaging probe.