Redox‐Responsive Gene Delivery from Perfluorocarbon Nanoemulsions through Cleavable Poly(2‐oxazoline) Surfactants

Estabrook, Daniel A.; Day, Rachael A.; Sletten, Ellen M.

doi:10.1002/anie.202102413

Cited by 17 publications

(11 citation statements)

References 55 publications

(23 reference statements)

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“…The combination of its ease of synthesis, its small size, and the relative strength and mobility of the fluorous effect makes R F -DNA a powerful tool in the self-assembly arsenal of structural DNA nanotechnology and may prove to be useful in the formation of functional assemblies that span into the micron-scale. Furthermore, interfacing fluorous-directed assembly of DNA nanostructures with other components could provide a molecular blueprint to enhance the delivery of biological components to specific cell types. − …”

Section: Discussionmentioning

confidence: 99%

Fluorous-Directed Assembly of DNA Origami Nanostructures

et al. 2022

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An orthogonal, noncovalent approach to direct the assembly of higher-order DNA origami nanostructures is described. By incorporating perfluorinated tags into the edges of DNA origami tiles we control their hierarchical assembly via fluorous-directed recognition. When we combine this approach with Watson−Crick base-pairing we form discrete dimeric constructs in significantly higher yield (8x) than when either molecular recognition method is used in isolation. This integrated "catch-and-latch" approach, which combines the strength and mobility of the fluorous effect with the specificity of base-pairing, provides an additional toolset for DNA nanotechnology, one that enables increased assembly efficiency while requiring significantly fewer DNA sequences. As a result, our integration of fluorous-directed assembly into origami systems represents a cheap, atom-efficient means to produce discrete superstructures.

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Section: Discussionmentioning

confidence: 99%

Fluorous-Directed Assembly of DNA Origami Nanostructures

et al. 2022

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“…This Account summarizes efforts in our lab over the past decade to develop next-generation FC NE cell detection probes. Next-generation FC-based cell detection probes will have improved sensitivity and specificity and be activatable and vector-capable, while retaining a focus on scalability and near-term translatability. Resulting probes will be effective for interrogating aspects of the initial biodistribution of cell therapy and inflammation detection.…”

Section: Discussionmentioning

confidence: 99%

Emergent Fluorous Molecules and Their Uses in Molecular Imaging

2021

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Metrics & More Article RecommendationsCONSPECTUS: This Account summarizes recent advances in the chemistry of fluorocarbon nanoemulsion (FC NE) functionalization. We describe new families of fluorous molecules, such as chelators, fluorophores, and peptides, that are soluble in FC oils. These materials have helped transform the field of in vivo molecular imaging by enabling sensitive and cell-specific imaging using magnetic resonance imaging (MRI), positron emission tomography (PET), and fluorescence detection. FC emulsions, historically considered for artificial blood substitutes, are routinely used for ultrasound imaging in clinic and have a proven safety profile and a well-characterized biodistribution and pharmacokinetics. The inertness of fluorocarbons contributes to their low toxicity but makes functionalization difficult. The high electronegativity of fluorine imparts very low cohesive energy density and Lewis basicity to heavily fluorinated compounds, making dissolution of metal ions and organic molecules challenging. Functionalization is further complicated by colloidal instability toward heat and pH, as well as limited availability of biocompatible surfactants.We have devised new fluorous chelators that overcome solubility barriers and are able to bind a range of metal ions with high thermodynamic stability and biocompatibility. NE harboring chelators in the fluorous phase are a powerful platform for the development of multimodal imaging agents. These compositions rapidly capture metal ions added to the aqueous phase, thereby functionalizing NEs in useful ways. For example, Fe 3+ encapsulation imparts a strong paramagnetic relaxation effect on 19 F T 1 that dramatically accelerates 19 F MRI data acquisition times and hence sensitivity in cell tracking applications. Alternatively, 89 Zr encapsulation creates a sensitive and versatile PET probe for inflammatory macrophage detection. Adding lanthanides, such as Eu 3+ , renders NE luminescent. Beyond chelators, this Account further covers our progress in formulating NEs with fluorophores, such as cyanine or BODIPY dyes, with their utility demonstrated in fluorescence imaging, biosensing, flow cytometry and histology. Fluorous dyes soluble in FC oils are also key enablers for nascent whole-body imaging technologies such as cryo-fluorescence tomography (CFT). Additionally, fluorous cell-penetrating peptides inserted on the NE surface increase the uptake of NE by ∼8fold in weakly phagocytic stem cells and lymphocytes used in immunotherapy, resulting in significant leaps in detection sensitivity in vivo.

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“…Higher levels of intracellular glutathione (GSH) as opposed to the extracellular microenvironment can also be employed to control gene release in the cytoplasmic matrix. 23 Although these endogenous biochemical signals have been used to develop responsive gene carriers, they are usually used to improve transfection efficiency and rarely achieve specific enrichment of genes in the lesion areas. 24 In addition, biochemical signals exist in both normal tissues and disease sites, and also are easily diffused, 25 making it difficult to achieve precise control of gene expression activity in spatial locations and even more difficult to achieve control in the temporal dimension.…”

Section: Introductionmentioning

confidence: 99%

Near-Infrared Photoresponsive Nanotransducers for Precise Regulation of Gene Expression

et al. 2023

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Regulation of gene expression is conducive to understanding the physiological roles of specific genes and provides therapeutic potentials, which however still remains a great challenge. Nonviral carriers have some advantages for gene delivery compared to traditional physical delivery strategies, but they often fail to control the delivery of genes in targeting regions, and thus lead to off-target side effects. Although endogenous biochemical signal-responsive carriers have been used to improve the transfection efficiency, their selectivity and specificity are still poor because of the coexistence of biochemical signals in both normal tissues and disease sites. In contrast, light-responsive carriers can be adopted to precisely control gene transgenic behaviors at the specified locations and time, thus reducing the off-target gene editing at nontarget positions. Particularly, the near-infrared (NIR) light has better tissue penetration depth and lower phototoxicity than ultraviolet and visible light sources, showing great promise for intracellular gene expression regulation. In this review, we summarize the recent progress of NIR photoresponsive nanotransducers for precision regulation of gene expression. These nanotransducers can achieve controlled gene expression via three different mechanisms (photothermal activation, photodynamic regulation, and NIR photoconversion) to allow various applications, such as gene therapy of cancer, which will be discussed in detail. A conclusion and discussion of the challenges and outlook will be given at the end of this review.

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Redox‐Responsive Gene Delivery from Perfluorocarbon Nanoemulsions through Cleavable Poly(2‐oxazoline) Surfactants

Cited by 17 publications

References 55 publications

Fluorous-Directed Assembly of DNA Origami Nanostructures

Fluorous-Directed Assembly of DNA Origami Nanostructures

Emergent Fluorous Molecules and Their Uses in Molecular Imaging

Near-Infrared Photoresponsive Nanotransducers for Precise Regulation of Gene Expression

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