Ionizable lipid nanoparticles for RAS protease delivery to inhibit cancer cell proliferation DOI
Ella Atsavapranee, Rebecca M. Haley, Margaret M. Billingsley

et al.

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 370, P. 614 - 625

Published: May 14, 2024

Language: Английский

Aminolysis of Highly Branched Poly(β-amino ester)s for Efficient mRNA Delivery DOI
Haiyang Yong, Zhili Li, Lixin Lin

et al.

Chemistry of Materials, Journal Year: 2025, Volume and Issue: unknown

Published: April 11, 2025

Language: Английский

Citations

0

Non-viral mRNA delivery to the lungs DOI Creative Commons

Lauren Healy,

B. Seto,

Haissi Cui

et al.

Biomaterials Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

This review highlights emerging strategies for lung-targeted mRNA delivery using non-viral vehicles, describing advances in bioinspired design and nanoparticle engineering.

Language: Английский

Citations

0

In vivomRNA delivery to the lung vascular endothelium by dicationic Charge-Altering Releasable Transporters DOI Creative Commons

Mahmoud M. AbdElwakil,

Jun Ni, Summer Ramsay-Burrough

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 19, 2025

Abstract Endothelial cells (EC) comprise the pulmonary vascular bed and play a significant role in health disease. Consequently, EC niche represents an attractive therapeutic target for treating wide range of diseases. We have identified new class dicationic Charge-Altering Releasable Transporters. These single-component transporters selectively deliver mRNA to lung upon intravenous administration without use targeting ligand. Significantly, number spatial array cationic charges within repeating units CART polymer are found control both delivery efficacy tissue tropism. High-resolution imaging revealed efficient endothelial arteries, veins capillaries. The selective tropism these CARTs, coupled with tunable synthesis this family amphiphiles, enabling platform research clinical applications.

Language: Английский

Citations

0

Polycations Improve Intracellular Stability of mRNA Delivered Using Lipid Nanoparticles for Prolonged Protein Expression DOI Creative Commons

Jumpei Norimatsu,

Rashida Hashim,

Theofilus A. Tockary

et al.

ACS Applied Nano Materials, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Language: Английский

Citations

0

Combination of Physicochemical Tropism and Affinity Moiety Targeting of Lipid Nanoparticles Enhances Organ Targeting DOI
Marco E. Zamora, Serena Omo‐Lamai, Manthan N. Patel

et al.

Nano Letters, Journal Year: 2024, Volume and Issue: unknown

Published: April 10, 2024

Two camps have emerged for targeting nanoparticles to specific organs and cell types: affinity moiety physicochemical tropism. Here we directly compare combine both using intravenous (IV) lipid (LNPs) designed target the lungs. We utilized PECAM antibodies as moieties cationic lipids These methods yield nearly identical lung uptake, but aPECAM LNPs show higher endothelial specificity. combining these had >2-fold uptake than either method alone markedly enhanced epithelial uptake. To determine if is because lungs are first organ downstream of IV injection, compared vs intra-arterial (IA) injection into carotid artery, finding that IA combined-targeting achieve 35% injected dose per gram (%ID/g) in first-pass organ, brain, among highest reported. Thus, strategies provides benefits neither achieves alone.

Language: Английский

Citations

3

Safer non-viral DNA delivery using lipid nanoparticles loaded with endogenous anti-inflammatory lipids DOI
Manthan N. Patel, Sachchidanand Tiwari, Yufei Wang

et al.

Nature Biotechnology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 5, 2025

Language: Английский

Citations

0

Probing the Role of Lipid Nanoparticle Elasticity on mRNA Delivery to the Placenta DOI
Hannah C. Safford,

Charles F. Shuler,

Hannah C. Geisler

et al.

Nano Letters, Journal Year: 2025, Volume and Issue: unknown

Published: March 14, 2025

It is well established that the physicochemical properties of lipid nanoparticles (LNPs) can govern their interactions with various biological barriers. One property hypothesized to influence nanoparticle-cell elasticity. Here, we formulate LNPs naturally occurring cholesterol analogs tune LNP elasticity and study its role on mRNA delivery placenta. was measured via atomic force microscopy where these exhibited Young's moduli ranging from 71.0 ± 26.2 411.4 145.7 kPa. In vitro screening in placental trophoblasts showed stiffer improved uptake compared softer LNPs. Following intravenous administration pregnant mice, incorporating β-sitosterol enhanced reduced liver containing only cholesterol. These results demonstrate ability promote highlight potential tuning improve LNP-mediated organs interest.

Language: Английский

Citations

0

Lipid Nanoparticles for In Vivo Lung Delivery of CRISPR-Cas9 Ribonucleoproteins Allow Gene Editing of Clinical Targets DOI
Rebecca M. Haley, Marshall S. Padilla, Rakan El‐Mayta

et al.

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: April 4, 2025

In the past 10 years, CRISPR-Cas9 has revolutionized gene-editing field due to its modularity, simplicity, and efficacy. It been applied for creation of in vivo models, further understand human biology, toward curing genetic diseases. However, there remain significant delivery barriers application clinic, especially extrahepatic applications. this work, high-throughput molecular barcoding techniques were used alongside traditional screening methodologies simultaneously evaluate LNP formulations encapsulating ribonucleoproteins (RNPs) vitro efficiency biodistribution. This resulted identification a lung-tropic formulation, which shows efficient gene editing endothelial epithelial cells within lung, targeting both model reporter clinically relevant genomic targets. Further, no off-target indel formation liver, making it highly specific system lung-editing

Language: Английский

Citations

0

Splenic B cell-targeting lipid nanoparticles for safe and effective mRNA vaccine delivery DOI Creative Commons
Yuichi Suzuki,

Mai Yakuwa,

Mina Sato

et al.

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: unknown, P. 113687 - 113687

Published: April 1, 2025

Language: Английский

Citations

0

Recent strategies for enhanced delivery of mRNA to the lungs DOI
Brittany J. Heiser, Arian Veyssi, Debadyuti Ghosh

et al.

Nanomedicine, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 27

Published: April 7, 2025

mRNA-based therapies have emerged as a transformative tool in modern medicine, gaining significant attention following their successful use COVID-19 vaccines. Delivery to the lungs offers several compelling advantages for mRNA delivery. The are one of most vascularized organs body, which provides an extensive surface area that can facilitate efficient drug transport. Local delivery bypasses gastrointestinal degradation, potentially enhancing therapeutic efficacy. In addition, capillary network ideal target systemic However, developing effective presents challenges. complex anatomy and body's immune response foreign particles create barriers This review discusses key approaches overcoming these challenges improving lungs. It examines both local strategies aimed at lung while mitigating off-target effects. Although substantial progress has been made lung-targeted therapies, remain optimizing cellular uptake achieving efficacy within pulmonary tissues. continued refinement enhance lung-specific targeting minimizing degradation is critical clinical success therapies.

Language: Английский

Citations

0