A Unimolecular Micelle Of PAMAM Based Star Polymer For Effective Cancer Treatment

As we all know,traditional chemotherapy is still one of the important methods of cancer treatment.With the development of cancer treatment,nanomedicines which comprised with nanocarriers and chemotherapy drugs appeared.Nanomedicines have received great attention,because they can solve the problems of poor water solubility and large side effects of drugs in vivo.According to their applicable environment,nano-drugs need to face various disruptive factors during the long-distance transportation in the body.Therefore,rigid requirements are proposed to the stability and size of nano-carriers.Based on the above,we developed a unimolecular micelle PAMAM-graft-PDEAEMA-block-PSBMA(PDS)with"core-shell-crown"structure and 3.0 GPAMAM was as core,giving the nanocarrier with long cycle stability and pH/thermo-sensitivity in vivo.Finally,we explored the application of PDS micelles in tumor treatment.Firstly,in this paper,DMAEMA and SBMA being as monomer,the star polymer PDS with PSBMA segments of different length was prepared by ATRP,called PDS_10/20/30/40.Structure and form of the polymers were characterized by FT-IR,¹H-NMR,DLS and TEM.DLS was used to track the change of the particle sizes of PDS micelles under different temperature and p H media,which measured maximum critical dissolution temperature(UCST)of PDS micelles.In order to investigate the stabilizing effect of PSBMA segment on PDS micelles,the size changes of PAMAM and PDS micelles were measured in different storage time,different protein solutions and different concentrations.Compared with PAMAM,PDS micelles performed excellent dispersive stability,which showed PDS has the potential to be used as a nanocarrier in organisms.According to these results of physicochemical characterization of PDS micelles,the DOX drug with cancer treatment was as a model drug,and loaded into micelles through"one-step method".The drug loading capacity(DLC)and drug release performance in vitro were studied in detail.CT26 liver cancer cells were as model cells,and the cytotoxicity of PDS micelles and the anticancer activity of DOX@PDS were studied by MTS,cell uptake and apoptosis experiments.These results of tumor suppression and ex vivo images with different tissues suggested that DOX@PDS not only prolonged the circulation time in the body,alleviated the problem of large side effects of free DOX,but also improved the effect of tumor suppression.It is expected that the research results will provide experimental basis for the design and research of new unimolecular micelles serving as nano-drug carriers.