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It is very challenging to fabricate a non-viral gene carrier system containing multifunctional components to overcome multiple extra- and intracellular barriers. Herein, we developed a novel PEGylated, targeted and fluorescence traceable multifunctional supramolecular host-guest gene vector system. This system was based on poly(β-cyclodextrin) (PCD), disulfide-containing azobenzene-terminated branched polymer (Az-ss-BPDM-RhB) with rhodamine-fluorescent functional groups and adamantyl terminated folate-modified PEG (Ad-PEG-FA). Transfection and cellular uptake data of the PEGylated supramolecular PCD/Az-ss-BPDM-RhB/DNA polyplexes demonstrated that prolonged incubation time to 24 h or longer could improve cell uptake and transfection efficiency of the PEGylated polyplexes. Good targeting and fluorescence traceable feature of this host-guest interaction gene delivery system was displayed. Moreover, the PEGylated and targeted supramolecular PCD/Az-ss-BPDM-RhB/Ad-PEG-FA showed lower cytotoxicity and  in vivo  zebrafish embryo toxicity and better gene transfection efficiency compared with the control 25 kDa PEI. Therefore, this PEGylated and targeted multifunctional supramolecular platform is a promising and effective gene delivery system for fluorescence traceable applications.

international journal of polymeric materials and polymeric biomaterials

Targeted and fluorescence traceable multifunctional host-guest supramolecular gene delivery platform based on poly(cyclodextrin) and rhodamine conjugated disulfide-containing azobenzene-terminated branched polymer