Biodegradable DNA‐Brush Block Copolymer Spherical Nucleic Acids Enable Transfection Agent‐Free Intracellular Gene Regulation

Zhang, Chuan; Hao, Liangliang; Calabrese, Colin M.; Zhou, Yu; Choi, Chung Hang Jonathan; Xing, Hang; Mirkin, Chad A.

doi:10.1002/smll.201501573

Cited by 75 publications

(87 citation statements)

References 44 publications

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“…By using various molar ratios, thiolated ssDNA and thiolated oligoethylene glycol strands to functionalize 13 nm gold (Au) cores to form SNAs of similar sizes, Giljohann et al previously observed a positive correlation between DNA loading density and intracellular delivery of Au‐cored SNAs to three cell types, including C166 endothelial cells, HeLa cells, and A549 lung cancer cells . Zhang et al arrived at a similar conclusion by preparing two sets of polymer‐cored SNAs with sizes of ≈40 nm, 1) micellar‐SNAs coated with DNA‐brush block copolymer (DBBC) strands (302 DNA strands per particle) and 2) micellar‐SNAs coated with linear block copolymer (LDBC) strands (190 DNA strands per particle) . The authors observed that DBCC–SNAs enter HeLa cells twice as much as LDBC–SNAs.…”

Section: Governing Factors Of the Cellular Uptake Of Dna Nanostructuresmentioning

confidence: 91%

Progress toward Understanding the Interactions between DNA Nanostructures and the Cell

Chiu

Choi

2019

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Advances in DNA nanotechnology empower the programmable assembly of DNA building blocks (oligonucleotides and plasmids) into DNA nanostructures with precise architectural control. As DNA nanostructures are biocompatible and can naturally enter mammalian cells without the aid of transfection agents, they have found numerous biological or biomedical applications as delivery carriers of therapeutic and imaging cargoes into mammalian cells for at least a decade. Nevertheless, mechanistic studies on how DNA nanostructures interact with cells have remained limited and incomprehensive until 2–3 years ago. This Review presents the recent progress in elucidating the “cell–nano” interactions of DNA nanostructures, with an emphasis on three key classes of structures commonly utilized in intracellular applications: tile‐based structures, origami‐based structures, and nanoparticle‐templated structures. Structural parameters of DNA nanostructures and strategies of biochemical modification for promoting intracellular delivery are discussed. Biological mechanisms for cellular uptake, including specific pathways and receptors involved, are outlined. Routes of intracellular trafficking and degradation, together with strategies for re‐directing their trafficking, are delineated. This Review concludes with several aspects of the “bio–nano” interactions of DNA nanostructures that warrant future investigations.

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Section: Governing Factors Of the Cellular Uptake Of Dna Nanostructuresmentioning

confidence: 91%

Progress toward Understanding the Interactions between DNA Nanostructures and the Cell

Chiu

Choi

2019

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“…For example, common block copolymer polymer vehicles such as poly(ethylene glycol)‐ block –poly(lactic‐ co ‐glycolic acid) (PEG–PLGA) used for targeted drug delivery have shown poor loading capacity for nucleic acids. While in recent years, Mirkin and co‐workers have pioneered the use of spherical nucleic acids for gene uptake and cells and regulation, many of these studies have primarily focused on building nucleic acid micellar or liposomal structures . To expand the materials set for co‐encapsulating nucleic acids and hydrophobic drugs within a single carrier, we report here the design and implementation of synthetic DNA analogs—namely click nucleic acids (CNAs)—for synthesizing PLGA‐based polymer nanoparticles that sequester high loadings of DNA.…”

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confidence: 99%

Synthesis and Assembly of Click‐Nucleic‐Acid‐Containing PEG–PLGA Nanoparticles for DNA Delivery

et al. 2017

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Co-delivery of both chemotherapy drugs and siRNA from a single delivery vehicle can have a significant impact on cancer therapy due to the potential for overcoming issues such as drug resistance. However, the inherent chemical differences between charged nucleic acids and hydrophobic drugs have hindered entrapment of both components within a single carrier. While poly(ethylene glycol)-block-poly(lactic-co-glycolic acid) (PEG-PLGA) copolymers have been used successfully for targeted delivery of chemotherapy drugs, loading of DNA or RNA has been poor. It is demonstrated that significant amounts of DNA can be encapsulated within PLGA-containing nanoparticles through the use of a new synthetic DNA analog, click nucleic acids (CNAs). First, triblock copolymers of PEG-CNA-PLGA are synthesized and then formulated into polymer nanoparticles from oil-in-water emulsions. The CNA-containing particles show high encapsulation of DNA complementary to the CNA sequence, whereas PEG-PLGA alone shows minimal DNA loading, and non-complementary DNA strands do not get encapsulated within the PEG-CNA-PLGA nanoparticles. Furthermore, the dye pyrene can be successfully co-loaded with DNA and lastly, a complex, larger DNA sequence that contains an overhang complementary to the CNA can also be encapsulated, demonstrating the potential utility of the CNA-containing particles as carriers for chemotherapy agents and gene silencers.

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“…The PEG was chosen in order to avoid the nonspecific adsorption of proteins at the particle surface and minimize the risk of masking the targeting FA moieties – in addition to its spacer function. In comparison to the polyester–DNA conjugates described above where additional PEG was applied only for the linear diblock copolymer (and not required for the more effective brush diblock copolymer), PEG has obviously a much larger effect if – as here – small molecules are attached to the polyester. Covalent conjugation was then successfully proven, for example, using GPC.…”

Section: Polyester Conjugation To Small Bioactive Moleculesmentioning

confidence: 99%

“…Synthesis: (A) polyester–peptide conjugates via azide click chemistry on alkyne‐grafted polyesters; (B) cRGD‐functionalized micelles via thiol click chemistry; (C) DNA block copolymers via click chemistry on PCL as graft (DBBC–SNA; top) and linear (LDBC–SNA; bottom) architectures …”

Section: Conjugates Of Biological Polymers (Nucleic Acids Peptides Amentioning

confidence: 99%

“…In this study, grafted DNA strands generated amphiphilic DBBC–SNA structures that assembled into micelles (upon solvent exchange) (Scheme (C); M w of PCL initiator = 14 kDa). These micelles exhibited a higher surface density of nucleic acids compared to other micelle structures that assembled from an analogous linear diblock copolymer (LDBC–SNA) via chain‐end functionalization (Scheme (C); yield of the conjugation step not specified) . DNA strands of the micelles were designed as an antisense sequence against enhanced green fluorescent protein (EGFP) mRNA, and after transfection and further incubation for 48 h, EGFP knockdown was readily apparent by fluorescence microscopy.…”

Section: Conjugates Of Biological Polymers (Nucleic Acids Peptides Amentioning

confidence: 99%

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Covalent polyester-biomolecule conjugates: advances in their synthesis and applications in biomedicine and nanotechnology

Winnacker

2017

Polym. Int.

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Among the variety of polymeric biomaterials, polyesters have a significant position, for example due to their biocompatibility and (tunable) biodegradability. In addition to their established and 'pristine' use as, for example, implants or sutures, the introduction of specific functional biomolecules to polyesters has been attracting increasing attention within the past few years to afford polyester-based functional bioconjugates, which require certain synthesis strategies. Selected recent concepts for these covalent conjugations are summarized in this article in terms of the attachment of biological macromolecules as well as small bioactive drugs on polyesters.

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Biodegradable DNA‐Brush Block Copolymer Spherical Nucleic Acids Enable Transfection Agent‐Free Intracellular Gene Regulation

Cited by 75 publications

References 44 publications

Progress toward Understanding the Interactions between DNA Nanostructures and the Cell

Progress toward Understanding the Interactions between DNA Nanostructures and the Cell

Synthesis and Assembly of Click‐Nucleic‐Acid‐Containing PEG–PLGA Nanoparticles for DNA Delivery

Covalent polyester-biomolecule conjugates: advances in their synthesis and applications in biomedicine and nanotechnology

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