Abstract
Drug/gene transportation systems with stimuli-responsive release behaviors are becoming research hotspots in biochemical and biomedical fields. In this work, a glucose-responsive supramolecular nanocluster was successfully constructed by the intermolecular complexation of phenylboronic acid modified β-cyclodextrin with adamantane modified polyethylenimine, which could be used as a biocompatible carrier for insulin and pCMV3-C-GFPSpark-Ins DNA which could express insulin co-delivery. Benefiting from the response capability of phenylboronic acid moiety toward glucose, the encapsulated insulin could be specifically released and the corresponding targeted DNA could efficiently express insulin in HepG2 cell, accompanied by the high-level insulin release in vitro. Our results demonstrate that the simultaneous insulin drug delivery and insulin gene transfection in a controlled mode may have great potential in the clinical diabetes treatments.
Highlights
(PEI), a traditional non-viral gene carrier with high buffer capacity, low immunogenicity, and satisfactory DNA loading capability has been considered as the golden standard of gene transfection[36] our designed glucose-responsive supramolecular nanocluster is considered as a potential drug and gene co-delivery system for the diabetes treatments
A weak interaction was observed between boronic acid and PEI (Fig. S11) and we can infer that this boronate–PEI interaction associated with host–guest complexation between CD and adamantane were jointly contributed to the formulation of PEI-Ada–PBCD assembly
Microscopic and gel electrophoresis investigations demonstrated that the PEI-Ada‒PBCD nanocluster exhibited high binding capability toward plasmid DNA (pDNA) and condensed them into uniform nanoparticles
Summary
(PEI), a traditional non-viral gene carrier with high buffer capacity, low immunogenicity, and satisfactory DNA loading capability has been considered as the golden standard of gene transfection[36] our designed glucose-responsive supramolecular nanocluster is considered as a potential drug and gene co-delivery system for the diabetes treatments. These results jointly indicate that the PEI-Ada‒PBCD complex could be formed through the noncovalent interactions between adamantyl groups of PEI-Ada and PBCD.
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