Bohemian Rhapsody of Future Drug Delivery Systems: Rational Changes Necessary for the Next Revolution DOI
Kinam Park, Andrew Otte, Tonglei Li

et al.

Molecular Pharmaceutics, Journal Year: 2024, Volume and Issue: unknown

Published: July 12, 2024

Controlled drug delivery technology has matured for more than 70 years, starting from a twice-a-day oral formulation to 6 month long-acting injectable formulations. Further technological advances require superior formulations treat various diseases efficiently. Developing future with practical innovations treating existing and new necessitates our continued efforts overcome at least three main hurdles. They include (i) reduced side effects, (ii) long-term treatment of chronic diseases, (iii) the overcoming biological barriers. Such start improved ability accurately test efficacy using proper controls. Future development can be aided by artificial intelligence if used properly. The next revolution systems will augmented implementation is given equal weight as discovery. process accelerated systemic revamp research funding structure cultivating generation scientists who think differently.

Language: Английский

Development of mRNA Lipid Nanoparticles: Targeting and Therapeutic Aspects DOI Open Access
Yaping Liu, Yingying Huang, Guantao He

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(18), P. 10166 - 10166

Published: Sept. 22, 2024

Lipid nanoparticles (LNPs) have emerged as leading non-viral carriers for messenger RNA (mRNA) delivery in clinical applications. Overcoming challenges safe and effective mRNA to target tissues cells, along with controlling release from the vehicle, remains pivotal mRNA-based therapies. This review elucidates structure of LNPs, mechanism delivery, targeted LNPs various cells tissues, including leukocytes, T-cells, dendritic Kupffer hepatic endothelial extrahepatic tissues. Here, we discuss applications mRNA-LNP vaccines prevention infectious diseases treatment cancer genetic diseases. Although remain terms efficiency, specific tissue targeting, toxicity, storage stability, technology holds extensive potential

Language: Английский

Citations

14
Tailoring Highly Branched Poly(β-amino ester)s for Efficient and Organ-Selective mRNA Delivery DOI
Haiyang Yong, Lixin Lin, Zhili Li

et al.

Nano Letters, Journal Year: 2024, Volume and Issue: 24(30), P. 9368 - 9376

Published: July 16, 2024

Development of mRNA therapeutics necessitates targeted delivery technology, while the clinically advanced lipid nanoparticles face difficulty for extrahepatic delivery. Herein, we design highly branched poly(β-amino ester)s (HPAEs) efficacious organ-selective through tailoring their chemical compositions and topological structures. Using an "A2+B3+C2" Michael addition platform, a combinatorial library 219 HPAEs with varied backbone structures, terminal groups, branching degrees are synthesized. The structures provide enhanced serum resistance significantly higher expression in vivo. amine determine organ-selectivity following systemic administration: morpholine facilitates liver targeting, ethylenediamine favors spleen delivery, methylpentane enables to liver, spleen, lungs simultaneously. This study represents comprehensive exploration structure–activity relationship governing both efficiency by HPAEs, suggesting promising candidates treating various organ-related diseases.

Language: Английский

Citations

10
Developing mRNA Nanomedicines with Advanced Targeting Functions DOI Creative Commons
Ji Wang, Lijun Cai, Ning Li

et al.

Nano-Micro Letters, Journal Year: 2025, Volume and Issue: 17(1)

Published: Feb. 21, 2025

The emerging messenger RNA (mRNA) nanomedicines have sprung up for disease treatment. Developing targeted mRNA has become a thrilling research hotspot in recent years, as they can be precisely delivered to specific organs or tissues enhance efficiency and avoid side effects. Herein, we give comprehensive review on the latest progress of with targeting functions. its carriers are first described detail. Then, mechanisms passive targeting, endogenous active outlined, focus various biological barriers that may encounter during vivo delivery. Next, emphasis is placed summarizing mRNA-based organ-targeting strategies. Lastly, advantages challenges clinical translation mentioned. This expected inspire researchers this field drive further development technology.

Language: Английский

Citations

1
Transfection via RNA-Based Nanoparticles: Comparing Encapsulation vs Adsorption Approaches of RNA Incorporation DOI

Amy E. Laturski,

Maria T. Dulay, Jillian L. Perry

et al.

Bioconjugate Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

Historically, RNA delivery via nanoparticles has primarily relied on encapsulation, as demonstrated by lipid in SARS-CoV-2 vaccines. Concerns about degradation nanoparticle surfaces initially limited the exploration of adsorption-based approaches. However, recent advancements have renewed interest adsorption a viable alternative. This Viewpoint explores approaches incorporation nanoparticles, comparing adsorption, and combination encapsulation presents framework to guide selection most suitable strategy based general characteristics.

Language: Английский

Citations

0
Peptides: Potential Delivery Systems for mRNA DOI Creative Commons

Huiting Liang,

Yun Xing, Kai Wang

et al.

RSC Chemical Biology, Journal Year: 2025, Volume and Issue: 6(5), P. 666 - 677

Published: Jan. 1, 2025

mRNA-based therapies have broad applications in various disease treatments and been applied protein replacement therapy, gene editing, vaccine development. Numerous research studies carried out aiming to increase the stability of mRNA, improve its translational efficiency, reduce immunogenicity. However, given mRNA's large molecular size strong electronegativity, safety efficient delivery mRNA into target cells remains critical rate-limiting step current drug Various nanocarriers, such as liposomes, lipid nanoparticles, polyetherimide, mesoporous silica employed for past few decades. Among them, peptides demonstrated great potential promising carrier candidates due their high cell membrane permeability, good biocompatibility, definite chemical structure, ease preparation. Here, peptide-based systems are systematically analyzed, including construction strategies, mechanisms action delivery, application limitations or challenges. It is hoped that this review will guide design, optimization, peptide carriers

Language: Английский

Citations

0
Inflammatory cytokines mediate the induction of and awakening from metastatic dormancy DOI Creative Commons
Paulo Pereira,

Joshua Panier,

Marc Nater

et al.

Cell Reports, Journal Year: 2025, Volume and Issue: 44(3), P. 115388 - 115388

Published: March 1, 2025

Highlights•T cells and IFNγ induce metastatic dormancy•T NK are dispensable for the maintenance of dormancy•IL-17A mediates awakening disseminated dormant cancer cellsSummaryMetastases arise from (DCCs) that detach primary tumor seed distant organs. There, quiescent DCCs can survive an extended time, a state referred to as dormancy. The mechanisms governing induction, maintenance, dormancy unclear. We show differentiation dormancy-inducing CD8+ T requires CD4+ cell help interferon (IFN)γ directly induces in DCCs. dormancy, however, is independent cells. Instead, inflammatory signal, we identified cell-derived interleukin (IL)-17A essential wake-up signal lungs. Thus, induction require external stimulus, while does not rely on continuous surveillance by lymphocytes.Graphical abstract

Language: Английский

Citations

0
A Comprehensive Review on Supramolecular Polymer Hydrogels for Localized and Long-Term Therapeutic Delivery DOI
Dilpreet Singh, Akshay Kumar

Journal of Macromolecular Science Part B, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 11

Published: March 3, 2025

Language: Английский

Citations

0
Predictive design of multimonomeric polyelectrolytes enables lung-specific gene delivery DOI
Jeffrey M. Ting, John D. Fisher,

Tyler Conyers

et al.

Polymer Chemistry, Journal Year: 2024, Volume and Issue: 15(26), P. 2627 - 2633

Published: Jan. 1, 2024

With a discovery engine combining polymer chemistry, biology, and AI, lung-specific pDNA delivery is demonstrated with single multimonomeric polyelectrolyte.

Language: Английский

Citations

1
Bohemian Rhapsody of Future Drug Delivery Systems: Rational Changes Necessary for the Next Revolution DOI
Kinam Park, Andrew Otte, Tonglei Li

et al.

Molecular Pharmaceutics, Journal Year: 2024, Volume and Issue: unknown

Published: July 12, 2024

Controlled drug delivery technology has matured for more than 70 years, starting from a twice-a-day oral formulation to 6 month long-acting injectable formulations. Further technological advances require superior formulations treat various diseases efficiently. Developing future with practical innovations treating existing and new necessitates our continued efforts overcome at least three main hurdles. They include (i) reduced side effects, (ii) long-term treatment of chronic diseases, (iii) the overcoming biological barriers. Such start improved ability accurately test efficacy using proper controls. Future development can be aided by artificial intelligence if used properly. The next revolution systems will augmented implementation is given equal weight as discovery. process accelerated systemic revamp research funding structure cultivating generation scientists who think differently.

Language: Английский

Citations

1