Construction Of Imaging Guided Multifunctional Anticancer Therapy Nanoplatform By Aromatic Amine Ring Opening Reaction

With the development of biomedical technology and better understanding of cancer pathology, many new anticancer approaches such as gene therapy and photodynamic therapy have been extensively investigated. Comparing with routine cancer therapy methods including surgery, chemotherapy and radiotherapy, these new strategies presented high anticancer efficiency and significantly improved biosafety by avoiding systemic side effects and cancer resistance. However, the therapeutic molecules and delivery systems with single function is insufficient to deal with complicated anticancer research nowadays. Herein,we proposed two different kind of multifunctional poly cation with imaging ability prepared by aromatic amine ring opening reaction as shown below:1. A series of star-like poly(glycidyl methacrylate) (PGMA)-based cationic vectors (II-PGEA/II) with abundant flanking polyhydric iodine units are prepared for multifunctional gene delivery systems by using ATRP and ring opening reaction. The proposed II-PGEA/II star vector is composed of one iohexol intermediate (?) core and five ethanolamine (EA)and ?-difunctionalized PGMA arms. The amphipathic ?-PGEA/? vectors readily self-assemble into well-defined cationic nanoparticles in aqueous media, where massive hydroxyl groups can establish a hydration shell to stabilize the nanoparticles. The ? introduction improves cell viabilities of polycations. Moreover, by controlling the suitable amount of introduced ?units, the resultant ?-PGEA/? nanoparticles can produce fairly good transfection performances in different cell lines. Most importantly, the ?-PGEA/II nanoparticles induce much better in vitro CT imaging abilities in tumor cells than iohexol (one commonly used commercial CT contrast agent). Further anticancer study mediated by ?-PGEA/?/pEGFP-CD suicide gene complex proved the possibility of CT guided high efficiency cancer therapy.2. In order to construct effective water-soluble multifunctional photosensitizers, series of star-like hydroxyl-rich polycations (Pc-PGEA/Pc) with flanking phthalocyanine (Pc) were prepared. The designed Pc-PGEA/Pc polycations consist of one Pc core and four EA and Pc-difunctionalized PGMA arms. The strong ?-? stacking and hydrophobicity of introduced Pc units drive the amphipathic Pc-PGEA/Pc to self-assemble into well-defined cationic nanoparticles. Such Pc-PGEA/Pc nanoparticles present impressive photodynamic therapy effects under moderate irradiation. Meanwhile, these nanoparticles also exhibit good performance as gene vectors. The photoacoustic imaging (PAI) ability given by the proper wavelength absorbance of Pc units provides one promising method for PAI-guided photodynamic/gene combined antitumor therapy. Based on these research results mentioned above, we have demonstrated that multifunctional polycations constructed by aromatic amine ring opening reaction could be used as high efficiency, low cytotoxicity and imaging visible anticancer agents. The experimental data obtained in these two projects would provide useful imformation for the developments of next generation anticancer agents.