1. Self‐Assembled Cationic Polypeptide Supramolecular Nanogels for Intracellular DNA Delivery
- Author
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Bart Jan Ravoo, Andrea Rentmeister, Sabine Hüwel, and Sharafudheen Pottanam Chali
- Subjects
polypeptides ,Biocompatibility ,Polymers ,Adamantane ,Supramolecular chemistry ,Nanogels ,macromolecular substances ,Conjugated system ,Catalysis ,Pyranine ,chemistry.chemical_compound ,ring opening polymerization ,Animals ,Humans ,chemistry.chemical_classification ,cyclodextrins ,Full Paper ,Cyclodextrin ,Organic Chemistry ,DNA ,General Chemistry ,Full Papers ,chemistry ,Biophysics ,Nanocarriers ,Peptides ,HeLa Cells ,N-carboxyanhydride ,Nanogel - Abstract
Supramolecular nanogels are an emerging class of polymer nanocarriers for intracellular delivery, due to their straightforward preparation, biocompatibility, and capability to spontaneously encapsulate biologically active components such as DNA. A completely biodegradable three‐component cationic supramolecular nanogel was designed exploiting the multivalent host‐guest interaction of cyclodextrin and adamantane attached to a polypeptide backbone. While cyclodextrin was conjugated to linear poly‐L‐lysine, adamantane was grafted to linear as well as star shaped poly‐L‐lysine. Size control of nanogels was obtained with the increase in the length of the host and guest polymer. Moreover, smaller nanogels were obtained using the star shaped polymers because of the compact nature of star polymers compared to linear polymers. Nanogels were loaded with anionic model cargoes, pyranine and carboxyfluorescein, and their enzyme responsive release was studied using protease trypsin. Confocal microscopy revealed successful transfection of mammalian HeLa cells and intracellular release of pyranine and plasmid DNA, as quantified using a luciferase assay, showing that supramolecular polypeptide nanogels have significant potential in gene therapy applications., Wrapped in a peptide box: Supramolecular nanogels self‐assembled from poly‐L‐lysine (PLL) modified with host and guest units can entrap molecular cargo such as DNA and deliver it into cells for transfection. The PLL is made by N‐carboxyanhydride polymerization and equipped with cyclodextrin and adamantane groups. The size of the nanogel can be tuned by the length of the PLL and smaller nanogels are better transfection agents.
- Published
- 2021