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Title: FGFR-targeted gene delivery mediated by supramolecular assembly between β-cyclodextrin-crosslinked PEI and redox-sensitive PEG
Authors: Ping, Y.
Hu, Q.
Tang, G.
Li, J. 
Keywords: FGFRs
Gene delivery
PEG detachment
Supramolecular self-assembly
Issue Date: Sep-2013
Citation: Ping, Y., Hu, Q., Tang, G., Li, J. (2013-09). FGFR-targeted gene delivery mediated by supramolecular assembly between β-cyclodextrin-crosslinked PEI and redox-sensitive PEG. Biomaterials 34 (27) : 6482-6494. ScholarBank@NUS Repository.
Abstract: A new redox-sensitive poly(ethylene glycol) (PEG)-based gene vector specially designed to target fibroblast growth factor receptors (FGFRs) was developed by host-guest supramolecular complexation. The new vector was designed as follows: 1) A host segment was consisted of β-cyclodextrin-crosslinked low molecular polyethylenimine (PEI) conjugated with MC11 peptide (MQLPLATGGGC) that can target FGFRs, being termed as MC11-PEI-β-cyclodextrin (MPC); 2) A guest segment is consisted of PEG and adamantyl group linked by a disulfide bond, the adamantyl-SS-PEG (Ad-SS-PEG); and 3) PEGylation of MPC by supramolecular complexation between MPC and Ad-SS-PEG to generate MPC/Ad-SS-PEG polycation, where the PEG chains can stabilize the DNA polyplexes extracellularly but can be readily cleavable intracellularly. It was found that the MPC/Ad-SS-PEG complexes could efficiently condense pDNA into nanoparticles around 100-200nm, and were able to effectively stabilize polyplexes against salt- or BSA-induced aggregation. The MPC/Ad-SS-PEG polyplexes were more readily to dissociate with the aid of heparin in the presence of 5m. m DTT. Invitro gene transfection and cytotoxicity experiments in different carcinoma cell lines expressing FGFRs showed that MPC/Ad-SS-PEG could mediate significantly higher transfection efficiency than MPC complexed with adamantyl-PEG (MPC/Ad-PEG), which has no disulfide linkage and is non-PEG-detachable. Furthermore, confocal laser scanning microscopy study indicated that MPC/Ad-SS-PEG polyplexes could mediate much more efficient endosomal escape than stably shield MPC/Ad-PEG polyplexes at 12h post-transfection. Importantly, MPC/Ad-SS-PEG was also able to efficiently mediate tumor-targeted gene delivery in the tumor-bearing mouse model after systemic injection invivo. These results suggest that the MPC/Ad-SS-PEG systems could be a safe and efficient non-viral vector for FGFR-mediated targeted gene delivery for cancer gene therapy. © 2013 Elsevier Ltd.
Source Title: Biomaterials
ISSN: 01429612
DOI: 10.1016/j.biomaterials.2013.03.071
Appears in Collections:Staff Publications

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