Construction And Performance Of Amphiphilic Binuclear-Ir(?)-Containing Metallohelicates

Cancer has been seriously threatening human's life and health and it is of great significance to explore newly effective means to treat cancer.Different from the traditional treatment approaches of chemotherapy and radiotherapy,photodynamic therapy(PDT)generally relies on the predominantly in situ generated reactive oxygen species(ROS)to irreversibly damage tumors when the photosensitizers are activated by light of a specific wavelength,which has been emerged as a promising cancer treatment with high spatial and temporal selectivity,minimal invasiveness,and negligible drug resistance.d~6-transition-metal ions containing,like Ir~?,triple-stranded helicates performed dramatic structure-inherent targeting abilities towards DNA and efficient PDT in spite of their poor water-solubility and biocompatibility.The key issues includes how to precisely modify the structures and design smart drug delivery systems,overcoming the limitations above,to enhance their PDT efficacy.In this article,neutral fac-Ir-PEG-CHO complex,appended with poly(ethylene glycol)(PEG),was selected as the building block to construct a series of amphiphilic binuclear triple helical structures by condensation them with the linear diamine linkers with different lengths.Importantly,their application in photodynamic threapy of cancers was preliminarily studied.The main results are as follows:(1)By using a stepwise hierarchical assembly approach,fac-Ir-PEG-CHO module was pre-synthesized and a series of binuclear triple helical structures with defined stereochemical informations were controllably synthesized by the condensation of aldehyde-group-decorated fac-Ir-PEG-CHO modules and linear alkanediamine linkers(1,2-ethylenediamine,EDA;1,3-propanediamine,PDA;1,4-butanediamine,BDA and 1,5-pentanediamine,PDA).Followed by reduction of the imine linkages,the relative amine-linked metallohelicates(H2b,M3b,H4b and M5b)showed high stabilities.These metallohelicates also performed long phosphorescent lifetime(1.6?1.9?s)and sensitizing singlet oxygen quantum yields(?s:41%?46%).(2)Nano drug delivery system was rationally designed for PDT study based on M5b-NPs,which was prepared with M5b by hydrophobic interactions.DLS,TEM and Zeta potential results indicated that M5b-NPs has suitable size,good particle dispersity and high structure stability.In the PDT study,nano drug delivery system performed remarkable singlet oxygen quantum generation ability and subcellular localization effect based on enhanced permeability and retention(EPR)and heavy atom effects,and the confocal imaging of photoinduced cell death and flow cytometry assay exhibited considerable cytotoxicity.