Self‐Assembled Cationic Polypeptide Supramolecular Nanogels for Intracellular DNA Delivery

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.

Supramolecular Hydrogels Based on Cyclodextrins: Progress and Perspectives

“…Recently our group presented the preparation of self‐assembled cationic polypeptide supramolecular nanogels and their application for intracellular DNA delivery [51a] . Nanogels were prepared by one pot, one step self‐assembly of three component system purely based on poly‐ L– Lysine (PLL) as a backbone (see Figure 7a).…”

“… (a) Design strategy of supramolecular CD−Ad nanogel based on poly‐ L– Lysine [51a] . The nanogels were loaded with DNA and their cellular uptake and release was studied using a luciferase assay.…”

“…The nanogels were loaded with DNA and their cellular uptake and release was studied using a luciferase assay. Reprinted with permission [51a] . Copyright 2021, Wiley‐VCH Verlag GmbH & Co. (b) (1) Schematic representation of amphiphilic and cationic copolymer with FA as targeting ligand.…”

A Simple Synthesis of Reduction-Responsive Acrylamide-Type Nanogels for miRNA Delivery

“…Among polymeric nanocarriers, the most exciting innovations in nanomedicine for gene delivery are nanogels, because they are biocompatible, possess high loading capacity, and have potential responsivity to environmental stimuli [ 10 , 11 ]. Recent studies have shown the promising use of synthetic nanogels as miRNA [ 12 , 13 , 14 , 15 , 16 , 17 ], siRNA [ 18 ], mRNA [ 19 ], and pDNA [ 20 ] delivery systems.…”

“…While the effectiveness of different miRNAs and their role as either oncogenes or tumor suppressors under certain conditions has been well established, many studies on synthetic smart nanogels have neglected to explicate the connection between miRNA loading capacity and release profile with different N/P ratios, either with or without the presence of biological stimuli [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ], which is the main focus of this study. In the current study, we developed biodegradable reduction-sensitive nanogels for miRNA encapsulating and enhancing miRNA release in a cancer-mimicking environment where the GSH level is elevated ( Figure 1 ).…”