Liposomes with Double-Stranded DNA Anchoring the Bilayer to a Hydrogel Core

Abstract

Liposomes are important biomolecular nanostructures for handling membrane-associated molecules in the lab and delivering drugs in the clinic. In addition to their biomedical applications, they have been widely used as model cell membranes in biophysical studies. Here we present a liposome-based model membrane that mimics the attachment of membrane-resident molecules to the cytoskeleton. To facilitate this attachment, we have developed a lipid-based hybrid nanostructure in which the liposome bilayer membrane is covalently anchored to a biocompatible poly(ethylene) glycol (PEG) hydrogel core using short double-stranded DNA (dsDNA) linkers. The dsDNA linkers connect cholesterol groups that reside in the bilayer to vinyl groups that are incorporated in the cross-linked hydrogel backbone. Size exclusion chromatography (SEC) of intact and surfactant-treated nanoparticles confirms the formation of anchored hydrogel structures. Transmission electron microscopy (TEM) shows ~100 nm nanoparticles even after removal of unanchored phospholipids. The location of dsDNA groups at the hydrogel-bilayer interface is confirmed with a fluorescence assay. Using DNA as a linker between the bilayer and a hydrogel core allows for temperature-dependent release of the anchoring interaction, produces polymer nanogels with addressible hybridization sites on their surface, and provides a prototype structure for potential future oligonucleotide drug delivery applications.

DNA Oligonucleotide-Functionalized Liposomes: Bioconjugate Chemistry, Biointerfaces, and Applications

“…The resulting duplex contained two terminal cholesterol units, which anchored more strongly into the lipid bilayer. In the literature, both monovalent and bivalent cholesterol anchors have been used, and single cholesterol anchors were more popular. , Cholesterol anchored DNAs have also been used for biosensing, DNA origami, drug delivery, and stimuli-responsive materials …”

“…In the literature, both monovalent and bivalent cholesterol anchors have been used, and single cholesterol anchors were more popular. 53,54 Cholesterol anchored DNAs have also been used for biosensing, 55 DNA origami, 56 drug delivery, 57 and stimuli-responsive materials. 58 Cholesterol anchors have noticeable effects on membrane stability.…”

Personalizing Biomaterials for Precision Nanomedicine Considering the Local Tissue Microenvironment

“…Hydrogels can prevent siRNA from inactivation during circulation while avoiding premature release. Consequently, gene delivery and RNAi‐based hydrogels were extensively reported using hydrogels composed of dextran‐PAMAM dendrimer, PEG, polyethyleneimine‐poly(organophosphazene), fibrin, chitosan/alginate for siRNA delivery or pullulan (polysaccharide polymer) and hyaluronic acid for DNA plasmid delivery . Although several studies reported the use of either hydrogel nanoparticles that enhance cancer cell sensitivity to chemotherapeutic agents or successful siRNA silencing, the majority of these studies reported only in vitro results.…”

Switchable conformational changes of DNA nanogel shells containing disulfide–DNA hybrids for controlled drug release and efficient anticancer action

“…They can be made of pure DNA [19][20][21][22] or DNA combined with other components. [23][24][25][26][27] It has been shown, that DNA nanogels can reveal the resistance to nuclease degradation, enhanced cellular uptake, and more effective drug-or siRNA delivery to cancer cells. Recently, it was shown, that CpG-rich oligonucleotide layers merged with nanoparticles act as a nanoimmunotherapeutic and introduce a robust antitumor immunity through a multi-pronged mechanism of neuroblastoma.…”