Self-assembly of size-controlled liposomes on DNA nanotemplates

Yang, Yang; Wang, Jing; Shigematsu, Hideki; Xu, Weiming; Shih, William M.; Rothman, James E.; Lin, Chenxiang

doi:10.1038/nchem.2472

Cited by 242 publications

(253 citation statements)

References 48 publications

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“…These results clearly demonstrate that the DNA gel skeleton is a stabilizer of the artificial cells. Yang et al (39) reported DNA nanorings as templates to prepare nanometer-sized liposomes inside. Meanwhile, our DNA cytoskeleton mechanically supported the micrometer-sized liposomes from the inside.…”

Section: Resultsmentioning

confidence: 99%

DNA cytoskeleton for stabilizing artificial cells

Kurokawa

Fujiwara

Morita

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

129

123

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Cell-sized liposomes and droplets coated with lipid layers have been used as platforms for understanding live cells, constructing artificial cells, and implementing functional biomedical tools such as biosensing platforms and drug delivery systems. However, these systems are very fragile, which results from the absence of cytoskeletons in these systems. Here, we construct an artificial cytoskeleton using DNA nanostructures. The designed DNA oligomers form a Y-shaped nanostructure and connect to each other with their complementary sticky ends to form networks. To undercoat lipid membranes with this DNA network, we used cationic lipids that attract negatively charged DNA. By encapsulating the DNA into the droplets, we successfully created a DNA shell underneath the membrane. The DNA shells increased interfacial tension, elastic modulus, and shear modulus of the droplet surface, consequently stabilizing the lipid droplets. Such drastic changes in stability were detected only when the DNA shell was in the gel phase. Furthermore, we demonstrate that liposomes with the DNA gel shell are substantially tolerant against outer osmotic shock. These results clearly show the DNA gel shell is a stabilizer of the lipid membrane akin to the cytoskeleton in live cells.iposomes have been used as artificial cell models to understand cell shape, membrane protein function, and lipid− protein interaction, among other biological functions (1-3). In addition, liposomes have been used as a platform for biosensing and as drug delivery systems (DDS) because of their excellent biocompatibility and biodegradability (4). However, liposomes collapse easily against environmental shifts and mechanical forces because of their low bending modulus. The fragility of liposomes causes uncontrolled leakage of the entrapped compounds and thus inhibits their use in biomedical applications and artificial cells experiments.In contrast, cell membranes are tolerant against environmental shifts and mechanical forces. The stability of cell membrane arises from the cytoskeleton underneath the membrane. The major component of cytoskeletons is actin (5). Actin gels show high elasticity (6), which ensures the stability of cell membranes against various forces. For liposomes, the use of actin filaments as a cytoskeleton is not an optimal strategy for the following three reasons: First, although actin bundles and actomyosin rings have been reconstituted in artificial cells (7,8), formation of an actin cortex underneath artificial membranes has been still challenging. Second, actin is hard to modify by chemical and genetic means because of its essentiality for cell growth. Third, the physicochemical properties of actin gels are still unclear (9, 10). Hence, the cytoskeleton of liposomes should be constructed with defined and designable materials. To accomplish this aim, DNA nanotechnology, which uses limited components with high designability in a nanometer scale (11), is a feasible candidate to construct cytoskeleton structures in artificial cells.DNA nanostructure...

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Section: Resultsmentioning

confidence: 99%

DNA cytoskeleton for stabilizing artificial cells

Kurokawa

Fujiwara

Morita

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

129

123

View full text Add to dashboard Cite

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“…15 DNA-assembled objects are of interest in the design and development of drug carriers, nanomachines, and other types of sophisticated nanomaterials. [16][17][18][19][20][21] The wide range of potential applications has led to considerable interest in the properties of oligonucleotides conjugated to polymers or lipophilic chains. [22][23][24][25][26][27][28][29][30] DNA conjugates often combine multiple self-assembly motifs enabling selective and orthogonal noncovalent interactions.…”

Section: Introductionmentioning

confidence: 99%

Pathway Diversity in the Self-Assembly of DNA-Derived Bioconjugates

Vyborna

Vybornyi²,

Häner

2016

Bioconjugate Chem.

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The pathway diversity of the self-assembly of amphiphilic DNA-pyrene conjugates is described.The hydrophobic pyrene units drive the self-assembly of the anionic oligomers in an aqueous environment into ribbon-shaped, DNA-grafted supramolecular polymers. Isothermal mixing of two types of sorted ribbons, each of which contains only one kind of two complementary oligonucleotides, results in the formation of tight networks. Thermal disassembly of these kinetically trapped networks and subsequent re-assembly of the liberated components leads to mixed supramolecular polymers, which now contain both types of oligonucleotides. The scrambling of the oligonucleotides prevents the interaction between ribbons and, thus, network formation. The results show that a high local density of DNA strands in linear arrays favors hybridization among sorted polymers, whereas hybridization among mixed arrays is prevented. The lack of DNA hybridization among mixed ribbons is ascribed to the electrostatic repulsion between identical, hence non-complementary, oligonucleotides. The findings highlight the importance of kinetically trapped states on the structural and functional properties of supramolecular polymers containing orthogonal self-assembly motifs.

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“…If the Ac-SOD enzymosome could be prepared with circular micro-reservoirs, it could be markedly ample for expressing its action without disruption and also for a sustained release pattern of the enzyme. Similar modifications are done for peptides and polymers which makes an important drug targeting pathway [62]. Therefore the Acenzymosome could be a replaceable therapeutic agent for an intense effect in rheumatoid arthritis and longer flowing active particles for reperfusion pathologies.…”

Section: Acylated-sod Liposomesmentioning

confidence: 99%

Enzymosomes: A Rising Effectual Tool for Targeted Drug Delivery System

et al. 2017

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The study aims to develop enzymosomes as an emerging novel drug delivery system for site-specific action. Enzymosomes utilises the specific nature of an enzyme, which is binding to a specific substrate at a controlled rate and catalysing product production step. An enzyme is encapsulated by coupling covalently to the surface of liposomes/lipid vesicles to form enzymosomes. Enzymes links through acylation, direct conjugation, physical adsorption, encapsulation methods to prepare enzymosomes with targeted action. Such novel drug delivery systems prove effective drug release and concomitantly reduces undesirable side effects of conventional treatment methods and hence showcase improvement in the long-term therapy of the disease. They are a promising substitute to conventional treatment therapies of gout, antiplatelet activities etc. Enzymosomes are newly designed supramolecular vesicular delivery systems to be useful as a tool in pharmaceutics for the raising of drug targeting and physicochemical properties and hence bioavailability. It shows beneficial effects of drugs with a narrow precision because targeting of these drugs to their site of action improves the drugs overall pharmacodynamics and pharmacokinetic profile. It also minimizes alterations in the normal enzymatic activity, thus enhancing half-life and achieve enzyme activity on targeted sites such as cancerous cells.

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Self-assembly of size-controlled liposomes on DNA nanotemplates

Cited by 242 publications

References 48 publications

DNA cytoskeleton for stabilizing artificial cells

DNA cytoskeleton for stabilizing artificial cells

Pathway Diversity in the Self-Assembly of DNA-Derived Bioconjugates

Enzymosomes: A Rising Effectual Tool for Targeted Drug Delivery System

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