Polymers Based On Metal-organic Frameworks Motif For Construction Of Gene And Drug Delivery Systems

Due to the properties of simple synthesis and high density of biocompatible terminal group,the dendritic catiomers were extensively studied in gene transfection and drug delivery to afford adequate colloidal stability in biological milieu and prolonged retention in blood circulation.The unique properties of dendrimers advocate themselves as promising platform for utilities in manufacture of gene and drug delivery systems.Ethanolamine(EA)functionalized poly(glycidyl methacrylate)(PGMA-EA)have been validated by our pioneering researches as promising materials for manufacture of gene delivery systems.Here,PGMA-EA was schemed to attach at the terminus of the MOF ligands for construction of nanoscaled dendritic catiomer.The resulting molecular structure was arranged to possess well-defined flanking secondary amine and hydroxyl groups,which consequently exerted drastic potency in DNA condensation(approximate 100 nm)and provided appreciable colloidal stability in the biological milieu.Of note,as compared to the commercial ‘gold standard' of branched PEI(25 kDa),the proposed catiomer exhibited markedly higher transfection efficiency by virtue of the appreciable cationic dendritic structure and lower cytotoxicity by virtue of rationale arrangement of hydroxyl groups.Therefore,the present work encouraged the utility of MOF-motif in engineering spatial functional and biological functional nanoscaled structure for biomedical applications.An aggregation-induced emission(AIE)molecule,tetraphenylethylene carboxylate derivative(TPE-(COOH)4),was synthesized and was used to aggregate with doxorubicin(Dox)to formulate the fluorescence nanoparticle(FN)base on aggregation of their hydrophobic component and electron interaction.Then,ethanediamine(EDA)functionalized PGMA with MOF(UiO-PGEDA)as an initiator was employed to complex with cucurbit[7]uril(CB[7])by means of host-guest interaction.The final product UiO-PGEDA-CB[7] has pH responsiveness in acidic environments.In order to further improve the stability,cell uptake and cancer cell targeting of FN,we combined FN with pH responsive UiO-PGEDA-CB[7] to form the complex of UiO-PGEDA-CB[7]/TPE-Dox.This complex nanosystem can control drug release in acidic environment.Morover,Dox release can be subsequently explored by the fluorescence resonance energy transfer(FRET)formed between Dox and TPE.Thus,the proposed system provide an important platform to pursue controlled drug release in acid environment and in situ tracing drug delivery.