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

Abstract

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.

Graphical Abstract

Keywords:

• Cationic polymeric gene vector
• fluorescence tracing
• gene therapy
• PEGylation

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This research was financially supported by the National Natural Science Foundation of China [51903020, 21875168, 21374083, 21674083 and 51533006], the Natural Science Foundation of Jiangsu Province [BK20190932 and BK20151249], the Changzhou Sci&Tech Program [CJ20190058].