Induction of Cytokines by Nucleic Acid Nanoparticles (NANPs) Depends on the Type of Delivery Carrier

Avila, Yelixza I.; Chandler, Morgan; Cedrone, Edward; Newton, Hannah S.; Richardson, Melina; Xu, Jie; Clogston, Jeffrey D.; Liptrott, Neill J.; Afonin, Kirill A.; Dobrovolskaia, Marina A.

doi:10.3390/molecules26030652

Cited by 29 publications

(47 citation statements)

References 66 publications

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“…Intriguingly, the induction of IL-8, MIP-1α, MCP-1, and RANTES was comparable between NANPs complexed with the lipid-based carrier and complexed with dendrimers. These results support the hypothesis that the type of carrier used for NANPs’ delivery significantly alters their ability to stimulate the immune response, both quantitatively and qualitatively [ 4 ].…”

Section: Delivery Method/carrier: An Unexpected Immunomodulatorsupporting

confidence: 83%

“…Due to the programmability and the intrinsic functions of nucleic acids, single-stranded DNA or RNA molecules are rationally designed into modular nucleic acid nanoparticles (NANPs) that are easily customized into supramolecular three-dimensional structures exclusively made of nucleic acids. RNA and DNA form canonical and non-canonical base pairings to assemble into various higher-order structures that serve as a basis for the assembly of different nanostructures including rings, fibers, and polygons [ 1 , 2 , 3 , 4 , 5 , 6 ]. Advantageously, the choice of nucleic acid components provides tunability for the physicochemical properties, biological activities, and multifunctionality of NANPs.…”

Section: Introductionmentioning

confidence: 99%

“…The modular functionalization of NANPs with aptamers, antibodies, or small molecules for their targeted delivery allows NANPs to integrate and deliver various TNAs into cells for synergistic therapeutic effects. However, despite these developments, NANPs have yet to advance to clinical translation due to concerns that need to be investigated and resolved including their specific delivery to target cells, their enzymatic degradation, and their ability to induce an immune response upon cellular uptake [ 4 , 12 , 14 , 15 ]. While targeting and stability are not immediate life-threatening issues, the excessive immune recognition of NANPs and overreaction by immune cells can have potentially deleterious effects.…”

Section: Introductionmentioning

confidence: 99%

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The Recognition of and Reactions to Nucleic Acid Nanoparticles by Human Immune Cells

et al. 2021

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The relatively straightforward methods of designing and assembling various functional nucleic acids into nanoparticles offer advantages for applications in diverse diagnostic and therapeutic approaches. However, due to the novelty of this approach, nucleic acid nanoparticles (NANPs) are not yet used in the clinic. The immune recognition of NANPs is among the areas of preclinical investigation aimed at enabling the translation of these novel materials into clinical settings. NANPs’ interactions with the complement system, coagulation systems, and immune cells are essential components of their preclinical safety portfolio. It has been established that NANPs’ physicochemical properties—composition, shape, and size—determine their interactions with immune cells (primarily blood plasmacytoid dendritic cells and monocytes), enable recognition by pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs) and RIG-I-like receptors (RLRs), and mediate the subsequent cytokine response. However, unlike traditional therapeutic nucleic acids (e.g., CpG oligonucleotides), NANPs do not trigger a cytokine response unless they are delivered into the cells using a carrier. Recently, it was discovered that the type of carrier provides an additional tool for regulating both the spectrum and the magnitude of the cytokine response to NANPs. Herein, we review the current knowledge of NANPs’ interactions with various components of the immune system to emphasize the unique properties of these nanomaterials and highlight opportunities for their use in vaccines and immunotherapy.

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Section: Delivery Method/carrier: An Unexpected Immunomodulatorsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Recognition of and Reactions to Nucleic Acid Nanoparticles by Human Immune Cells

et al. 2021

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“…Images were processed by FemtoScan Online software package (Advanced Technologies Center, Moscow, Russia). [ 80,81 ]…”

Section: Methodsmentioning

confidence: 99%

Anhydrous Nucleic Acid Nanoparticles for Storage and Handling at Broad Range of Temperatures

Tran

Chandler

Halman

et al. 2022

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Recent advances in nanotechnology now allow for the methodical implementation of therapeutic nucleic acids (TNAs) into modular nucleic acid nanoparticles (NANPs) with tunable physicochemical properties which can match the desired biological effects, provide uniformity, and regulate the delivery of multiple TNAs for combinatorial therapy. Despite the potential of novel NANPs, the maintenance of their structural integrity during storage and shipping remains a vital issue that impedes their broader applications. Cold chain storage is required to maintain the potency of NANPs in the liquid phase, which greatly increases transportation costs. To promote long‐term storage and retention of biological activities at higher temperatures (e.g., +50 °C), a panel of representative NANPs is first exposed to three different drying mechanisms—vacuum concentration (SpeedVac), lyophilization (Lyo), and light‐assisted drying (LAD)—and then rehydrated and analyzed. While SpeedVac primarily operates using heat, Lyo avoids temperature increases by taking advantage of pressure reduction and LAD involves a near‐infrared laser for uniform drying in the presence of trehalose. This work compares and defines refinements crucial in formulating an optimal strategy for producing stable, fully functional NANPs and presents a forward advancement in their development for clinical applications.

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“…For example, variations in shape, size, and composition of nucleic acid nanoparticles induce distinct immunostimulatory profiles [221]. Recent studies have described how the nanosized carrier employed for delivery provides an additional means to tailor nanomedicine immunorecognition (e.g., lipid-based platform versus dendrimers display differences in cytokine induction) [222].…”

Section: Pre-clinical Pharmacology and Toxicology Studiesmentioning

confidence: 99%

Current hurdles to the translation of nanomedicines from bench to the clinic

Đorđević

Medel

Conejos‐Sánchez

et al. 2021

Drug Deliv. and Transl. Res.

165

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The field of nanomedicine has significantly influenced research areas such as drug delivery, diagnostics, theranostics, and regenerative medicine; however, the further development of this field will face significant challenges at the regulatory level if related guidance remains unclear and unconsolidated. This review describes those features and pathways crucial to the clinical translation of nanomedicine and highlights considerations for early-stage product development. These include identifying those critical quality attributes of the drug product essential for activity and safety, appropriate analytical methods (physical, chemical, biological) for characterization, important process parameters, and adequate pre-clinical models. Additional concerns include the evaluation of batch-to-batch consistency and considerations regarding scaling up that will ensure a successful reproducible manufacturing process. Furthermore, we advise close collaboration with regulatory agencies from the early stages of development to assure an aligned position to accelerate the development of future nanomedicines. Graphical abstract

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Induction of Cytokines by Nucleic Acid Nanoparticles (NANPs) Depends on the Type of Delivery Carrier

Cited by 29 publications

References 66 publications

The Recognition of and Reactions to Nucleic Acid Nanoparticles by Human Immune Cells

The Recognition of and Reactions to Nucleic Acid Nanoparticles by Human Immune Cells

Anhydrous Nucleic Acid Nanoparticles for Storage and Handling at Broad Range of Temperatures

Current hurdles to the translation of nanomedicines from bench to the clinic

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