Modular delivery of CpG-incorporated lipid-DNA nanoparticles for spleen DC activation

Jin, Jun‐O; Haein, Park; Zhang, Wei; Vries, Jan Willem de; Gruszka, Agnieszka; Lee, Myung Won; Ahn, Dae‐Ro; Herrmann, Andreas; Kwak, Minseok

doi:10.1016/j.biomaterials.2016.11.020

Cited by 48 publications

(48 citation statements)

References 44 publications

(37 reference statements)

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“…Although studies have shown that CpG can induce spleen DC activation [34,35], the role of CpG-conjugated DNA nanoobjects in spleen DCs in vivo has not been well characterized. Jin et al have successfully used DNA-lipid micelle nanoparticles for in vivo immune stimulation (Jin et al, 2017). The lipidmodified nucleotides and fluorescent probes are incorporated into the DNA strand to form uniform-sized DNA-lipid micelle particles, and the CpG-conjugated nanoparticles induce significant up-regulation of stimulator DC-derived stimulating molecules and cytokines.…”

Section: Hybrid Dna-based Nanoparticlesmentioning

confidence: 99%

“…DNA nanostructures bind to these therapeutic molecules in immunotherapy. Due to its high degree of structural programmability, permeability, and biocompatibility, DNA nanostructures are among the most promising candidates for delivery of immune pharmaceuticals (Jin et al, 2017;Yang et al, 2019). In our previous studies, we paid attention to the biophysical aspect of the structure as a kind of biomacromolecule (Chi and Jiang, 2012;Chi et al, 2013), the molecular mechanism of immunomodulation and immunotherapy of small molecule drugs (Tian et al, 2015;Chai et al, 2016;.…”

Section: Introductionmentioning

confidence: 99%

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DNA Nanostructure as an Efficient Drug Delivery Platform for Immunotherapy

Chi

Yang

et al. 2020

Front. Pharmacol.

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Immunotherapy has received increasing attention due to its low potential side effects and high specificity. For instance, cancer immunotherapy has achieved great success. CpG is a well-known and commonly used immunotherapeutic and vaccine adjuvant, but it has the disadvantage of being unstable and low in efficacy and needs to be transported through an effective nanocarrier. With perfect structural programmability, permeability, and biocompatibility, DNA nanostructures are one of the most promising candidates to deliver immune components to realize immunotherapy. However, the instability and low capability of the payload of ordinary DNA assemblies limit the relevant applications. Consequently, DNA nanostructure with a firm structure, high drug payloads is highly desirable. In the paper, the latest progress of biostable, high-payload DNA nanoassemblies of various structures, including cage-like DNA nanostructure, DNA particles, DNA polypods, and DNA hydrogel, are reviewed. Cage-like DNA structures hold drug molecules firmly inside the structure and leave a large space within the cavity. These DNA nanostructures use their unique structure to carry abundant CpG, and their biocompatibility and size advantages to enter immune cells to achieve immunotherapy for various diseases. Part of the DNA nanostructures can also achieve more effective treatment in conjunction with other functional components such as aPD1, RNA, TLR ligands.

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Section: Hybrid Dna-based Nanoparticlesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

DNA Nanostructure as an Efficient Drug Delivery Platform for Immunotherapy

Chi

Yang

et al. 2020

Front. Pharmacol.

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Section: Applicationsmentioning

confidence: 99%

DNA Nanotechnology Enters Cell Membranes

Huo

Boersma

et al. 2019

Advanced Science

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DNA is more than a carrier of genetic information: It is a highly versatile structural motif for the assembly of nanostructures, giving rise to a wide range of functionalities. In this regard, the structure programmability is the main advantage of DNA over peptides, proteins, and small molecules. DNA amphiphiles, in which DNA is covalently bound to synthetic hydrophobic moieties, allow interactions of DNA nanostructures with artificial lipid bilayers and cell membranes. These structures have seen rapid growth with great potential for medical applications. In this Review, the current state of the art of the synthesis of DNA amphiphiles and their assembly into nanostructures are first summarized. Next, an overview on the interaction of these DNA amphiphiles with membranes is provided, detailing on the driving forces and the stability of the interaction. Moreover, the interaction with cell surfaces in respect to therapeutics, biological sensing, and cell membrane engineering is highlighted. Finally, the challenges and an outlook on this promising class of DNA hybrid materials are discussed.

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“…Thus, in the self-assembly field, molecular TLR agonists are of great interest. Some of these studies are investigating how the shape of carriers used to deliver TLR ligands [56] , or the tunable surface display of TLR ligands [63] , [64] , [65] , impacts the degree of DC activation and the cytokine secretion profiles. As discussed in Section 4 , DNA sequences can be finely tuned to form defined structures, enabling control over the organization and spacing of tertiary features.…”

Section: Self-assembled Systems Can Create Design Guidelines For New mentioning

confidence: 99%

“…One example of an approach to modulate responses in clinically-relevant contexts has been to incorporate molecular adjuvants into self-assembled materials. CpG has been incorporated into multiple self-assembled nanoparticle formulations, through non-covalent interactions with lipids [64] , gold nanoparticles [63] , [124] , or synthetic polymers [125] . Broadly, these strategies aim to enhance circulation time as well as target CpG to target cell populations – APCs, like dendritic cells – through nanoparticle-mediated delivery.…”

Section: Pre-clinical Studies Using Self-assembled Materials Demonstrmentioning

confidence: 99%

Engineering self-assembled materials to study and direct immune function

Tostanoski

Jewell

2017

Advanced Drug Delivery Reviews

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The immune system is an awe-inspiring control structure that maintains a delicate and constantly changing balance between pro-immune functions that fight infection and cancer, regulatory or suppressive functions involved in immune tolerance, and homeostatic resting states. These activities are determined by integrating signals in space and time; thus, improving control over the densities, combinations, and durations with which immune signals are delivered is a central goal to better combat infectious disease, cancer, and autoimmunity. Self-assembly presents a unique opportunity to synthesize materials with well-defined compositions and controlled physical arrangement of molecular building blocks. This review highlights strategies exploiting these capabilities to improve the understanding of how precisely-displayed cues interact with immune cells and tissues. We present work centered on fundamental properties that regulate the nature and magnitude of immune response, highlight pre-clinical and clinical applications of self-assembled technologies in vaccines, cancer, and autoimmunity, and describe some of the key manufacturing and regulatory hurdles facing these areas.

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Modular delivery of CpG-incorporated lipid-DNA nanoparticles for spleen DC activation

Cited by 48 publications

References 44 publications

DNA Nanostructure as an Efficient Drug Delivery Platform for Immunotherapy

DNA Nanostructure as an Efficient Drug Delivery Platform for Immunotherapy

DNA Nanotechnology Enters Cell Membranes

Engineering self-assembled materials to study and direct immune function

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