High-Throughput <i>In Vivo</i> Screening Identifies Differential Influences on mRNA Lipid Nanoparticle Immune Cell Delivery by Administration Route

Hamilton, Alex G.; Swingle, Kelsey L.; Thatte, Ajay S.; Mukalel, Alvin J.; Safford, Hannah C.; Billingsley, Margaret M.; El-Mayta, Rakan D.; Han, Xuexiang; Nachod, Benjamin E.; Joseph, Ryann A.; Metzloff, Ann E.; Mitchell, Michael J.

doi:10.1021/acsnano.4c01171

ACS Nano

2024

DOI: 10.1021/acsnano.4c01171

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High-Throughput In Vivo Screening Identifies Differential Influences on mRNA Lipid Nanoparticle Immune Cell Delivery by Administration Route

Alex G. Hamilton,

Kelsey L. Swingle,

Ajay S. Thatte

et al.

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2024

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Cited by 5 publications

References 81 publications

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In Vivo Screening of Barcoded Gold Nanoparticles Elucidates the Influence of Shapes for Tumor Targeting

Huang,

Le,

et al. 2024

Adv Funct Materials

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Gold nanoparticles (NPs) are promising for cancer therapy due to their versatile shapes, optical properties, adjustable sizes, and facile functionalization. However, their diverse physicochemical properties, complex in vivo environments, and cellular heterogeneity lead to markedly different interactions with cells, impacting reproducibility and application selection. To address this, we implemented a DNA barcoding system to label gold NPs with varying shapes, sizes, and surface modifications for tumor delivery optimization. Six NP species, comprising three shapes (sphere, rod, triangle) and two sizes (40 nm, 80 nm), were tagged with unique DNA barcodes. Barcodes demonstrated minimal detachment, no interference with cell interactions, and resistance to DNase digestion. Next‐generation sequencing revealed that sphere NPs exhibited poor in vitro uptake but superior in vivo tumor targeting, likely due to enhanced endothelial interactions and reduced macrophage clearance. Additionally, 80 nm nanotriangles displayed excellent tumor targeting both in vitro and in vivo. Supporting experiments validated these findings. To demonstrate practical utility, the NPs were applied in siRNA delivery and photothermal therapy in a breast tumor model. This study pioneers the integration of DNA barcoding with gold NPs to systematically explore shape, size, and surface modifications for in vivo delivery.

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In Vivo Screening of Barcoded Gold Nanoparticles Elucidates the Influence of Shapes for Tumor Targeting

Huang,

Le,

et al. 2024

Adv Funct Materials

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Innovation of Lipid‐Based Nanoparticles: the Design and Applications in the Cardiovascular Disease Management

Gu,

Liu,

Rao

et al. 2024

Adv Funct Materials

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Cardiovascular diseases (CVDs) represent a prominent cause of global mortality, posing considerable challenges for traditional therapies due to their limited bioavailability and notable side effects. Similarly, imaging diagnostic modalities have inherent limitations. Lipid‐based nanoparticles (LNPs) have emerged as promising tools for precise diagnosis and treatment of CVDs, owing to their exceptional biocompatibility, modifiability, and compatibility with payloads, showcasing extensive potential for diverse applications. LNPs excel in encapsulating diverse drug compounds, protecting against drug degradation, and enabling targeted drug delivery at lesion sites. Moreover, in conjunction with multimodal imaging techniques, LNPs enhance the accuracy of diagnosing and treating CVDs. Nevertheless, this field lacks comprehensive and up‐to‐date reviews. Therefore, this review delineates the foundational principles governing nano‐strategies employing LNP systems for addressing CVDs. It explores recent advancements in utilizing these strategies for diagnosing and treating different cardiovascular conditions while also pointing out their limitations. This review aims to provide insights for future research endeavors.

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Peptide-Functionalized Lipid Nanoparticles for Targeted Systemic mRNA Delivery to the Brain

Han,

Tang,

Kim

et al. 2024

Nano Lett.

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Systemic delivery of large nucleic acids, such as mRNA, to the brain remains challenging in part due to the bloodbrain barrier (BBB) and the tendency of delivery vehicles to accumulate in the liver. Here, we design a peptide-functionalized lipid nanoparticle (LNP) platform for targeted mRNA delivery to the brain. We utilize click chemistry to functionalize LNPs with peptides that target receptors overexpressed on brain endothelial cells and neurons, namely the RVG29, T7, AP2, and mApoE peptides. We evaluate the effect of LNP targeting on brain endothelial and neuronal cell transfection in vitro, investigating factors such as serum protein adsorption, intracellular trafficking, endothelial transcytosis, and exosome secretion. Finally, we show that LNP peptide functionalization enhances mRNA transfection in the mouse brain and reduces hepatic delivery after systemic administration. Specifically, RVG29 LNPs improved neuronal transfection in vivo, establishing its potential as a nonviral platform for delivering mRNA to the brain.

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High-Throughput In Vivo Screening Identifies Differential Influences on mRNA Lipid Nanoparticle Immune Cell Delivery by Administration Route

Cited by 5 publications

References 81 publications

In Vivo Screening of Barcoded Gold Nanoparticles Elucidates the Influence of Shapes for Tumor Targeting

In Vivo Screening of Barcoded Gold Nanoparticles Elucidates the Influence of Shapes for Tumor Targeting

Innovation of Lipid‐Based Nanoparticles: the Design and Applications in the Cardiovascular Disease Management

Peptide-Functionalized Lipid Nanoparticles for Targeted Systemic mRNA Delivery to the Brain

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