Fast, Efficient, and Targeted Liposome Delivery Mediated by DNA Hybridization

Abstract

Safety and efficacy, two significant parameters in drug administration, can be improved by site‐specific delivery approaches. Here a fast, efficient, and targeted liposome delivery system steered by a DNA hybridization recognition mechanism is presented. For this purpose, lipid‐terminated DNA is inserted in both liposome and cell membranes by simple mixing of the components. Cellular accumulation of cargo encapsulated in the liposomal core is substantially enhanced when the DNA sequence on the cell is complementary to that on the liposome. Additionally, in mixed cell populations, liposomes discriminate targets by their complementary DNA sequences. Exposure of cells to low temperature and endocytosis inhibitors suggests a caveolae‐dependent endocytosis uptake pathway. Mechanistically, hybridization between DNA strands spatially traps liposomes and cell membranes in close proximity, consequently increases the local liposome concentration, and thereby enhances cellular uptake of liposomes and their payload. This programmable delivery system might contribute to new applications in molecular biology and drug delivery.

Thermo‐Sensitive Dual‐Functional Nanospheres with Enhanced Lubrication and Drug Delivery for the Treatment of Osteoarthritis

“…[16] Biocompatible nanoparticles, liposomes, and hydrogels are commond rug carriers to achievet argeted and controlled drug delivery. [17,18] In previouss tudies, we have used mesoporous silica nanoparticles andd istearoyl phosphocholine liposomes to encapsulate typical anti-inflammatory drugs for the treatment of osteoarthritis through intra-articular injection to the joint. [19,20] Although these nanocarriers have shown effective outcomes with good biocompatibility,t hey are unable to respond quickly under externale nvironmental stimulation.…”

Recent Progress of DNA Nanostructures on Amphiphilic Membranes

“…This improved modification strategy led to a highly stable insertion of DNA and thus a more effective full fusion of vesicles. What's more, apart from the fusion between liposomes, drugs, [ 152 ] and nanostructures [ 153 ] such as DNA tetrahedrons, gold (Au) NPs, and polystyrene (PS) NPs were delivered to the cell by using the nucleobase quadruple‐anchored DNA.…”

Recent Advances of DNA Nanostructure‐Based Cell Membrane Engineering

“…In fact, except DNA origami, ssDNA also provides a powerful tool for studying the membrane‐fusion process [ 57,88–90 ] and the exchange of material between liposomes and cells. [ 131,132 ] Our group reported a DNA‐programmed membrane fusion strategy for guiding the efficient intracellular delivery of proteins into live cells in 2018. [ 131 ] The inherent programmability of DNA hybridization allows scientists to control membrane fusion spatiotemporally.…”

“…Similarly, Herrmann and co‐workers reported a targeted liposome delivery system to living cells through DNA hybridization in 2019. [ 132 ] First, liposomes and cell membranes were spatially trapped. Then, the increase of local liposome concentration results in the enhanced cellular uptake of liposome vehicles and their payload.…”