Enhancing RNA Delivery: Practical Insights into NeoLNP™ Transfection Reagent DOI Open Access

Xiaobao Chen,

Yan Wu,

Li Liu

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 12, 2024

Abstract The rapid advancement of RNA-based therapeutics, particularly in the wake COVID-19 vaccine success, has prompted significant research into optimizing RNA delivery mechanisms. This study evaluates NeoLNP™ Transfection Kit developed by Scindy Pharmaceutical, which utilizes lipid nanoparticles (LNPs) for efficient encapsulation and delivery. We systematically investigate various parameters affecting transfection efficiency, including concentration, RNA/LNP volume ratios, mixing techniques, LNP stability, culture media. Our results demonstrate that optimal concentration efficiency is around 40-60 ng/µL, with a 1:0.75-1:1 RNA-to-LNP ratio yielding highest protein expression. Additionally, we find gentle techniques outperform harsher methods, stability LNP-RNA complexes significantly influences outcomes. provides practical guidelines enhancing paving way more effective therapeutics.

Language: Английский

RNA-based therapies in liver metabolic diseases DOI Creative Commons
Antonio Fontanellas, Pedro Berraondo, F Urigo

et al.

Gut, Journal Year: 2025, Volume and Issue: unknown, P. gutjnl - 331742

Published: Feb. 23, 2025

RNA-based therapeutics have rapidly emerged over the past decade, offering a new class of medicines that differ significantly from conventional drugs. These therapies can be programmed to target or restore defective genes, allowing for more personalised treatments and reducing side effects. Notably, RNA made significant progress in treatment genetic liver diseases, exemplified by small interfering hereditary transthyretin amyloidosis, which use liver-targeting strategies such as GalNAc conjugation improve efficacy safety. gene-editing technologies, base editor prime clustered regularly interspaced short palindromic repeats systems, also show promise with their ability minimise genomic rearrangements cancer risk. While offer high precision, challenges remain optimising delivery methods ensuring long-term safety efficacy. Lipid nanoparticle-mRNA therapeutics, particularly protein replacement rare gained support preclinical successes. Compared viral gene therapies, mRNA present safer profile reduced risks integration oncogene activation. However, clinical trials, especially face limitations sample sizes observation periods. Further studies, including non-human primates, will essential refining trial designs. Despite potential, costs pose challenge require cost–utility models guide pricing accessibility. Here, we discuss fundamental aspects showcase most relevant developments metabolic diseases.

Language: Английский

Citations

1
Capturing the Dynamic Integrity of Carbocyanine Fluorophores-based Lipid Nanoparticles by the FRET technique DOI Creative Commons
Siyu Long, David A. Turner, Kevin J. Hamill

et al.

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

Published: Jan. 1, 2025

Nanoparticles capable of dynamically reporting their structural integrity in real-time are a powerful tool to guide the design drug delivery technologies.

Language: Английский

Citations

0
Nanodrug Delivery System for Precision Treatment of Pulmonary Fibrosis DOI Creative Commons
Xianhao Yi, Xinru Zhang, Y. Guan

et al.

Precision medicine and engineering., Journal Year: 2025, Volume and Issue: unknown, P. 100025 - 100025

Published: March 1, 2025

Language: Английский

Citations

0
Discovery of a Novel Selective PAK1/HDAC6/HDAC10 Inhibitor ZMF-25 that Induces Mitochondrial Metabolic Breakdown and Autophagy-Related Cell Death in Triple Negative Breast Cancer DOI Creative Commons
Jin Zhang, Xiaoling Cheng, Gang Chen

et al.

Research, Journal Year: 2025, Volume and Issue: 8

Published: Jan. 1, 2025

Triple-negative breast cancer (TNBC) is the most aggressive subtype, and addressing its intrinsic heterogeneity has emerged as a valuable avenue for novel clinical treatment strategy. Here, we put forward an innovative strategy TNBC by simultaneously suppressing both p21-activated kinase 1 (PAK1) histone deacetylase (HDAC) class IIb (HDAC6/10). A series of pyrido [2,3-d]pyrimidin-7(8 H )-one moiety derivatives was successfully designed synthesized to target PAK1/HDAC6/HDAC10 utilizing structure-based screening pharmacophore integration. ZMF-25 demonstrates marked inhibitory activity against PAK1, HDAC6, HDAC10 with respective IC 50 values 33, 64, 41 nM, remarkable selectivity over HDACs PAKs, well prominent antiproliferative efficiency in MDA-MB-231 cells. Additionally, effectively suppresses proliferation migration inhibiting PAK1/HDAC6/HDAC10. Moreover, it found impair glycolysis trigger reactive oxygen species generation, resulting autophagy-related cell death AKT/mTOR/ULK1 signaling. Furthermore, exhibits therapeutic potential no obvious toxicity vivo good pharmacokinetics. In summary, these observations indicate that potent triple-targeting inhibitor, which expected provide effective treatment.

Language: Английский

Citations

0
Dimethylamino-based synthetic lipidoid nanoparticles for selective mRNA delivery to splenic antigen-presenting cells DOI
Liang Xue, Chenchen Zhang, Qi Yin

et al.

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: unknown, P. 113737 - 113737

Published: April 1, 2025

Language: Английский

Citations

0
Biocompatible lipid nanovehicles for preventive and therapeutic vaccine development DOI

Yaru Jia,

Ziran Zhou,

Luksika Jiramonai

et al.

Coordination Chemistry Reviews, Journal Year: 2025, Volume and Issue: 538, P. 216718 - 216718

Published: April 22, 2025

Language: Английский

Citations

0
Revolutionizing Nanovaccines: A New Era of Immunization DOI Creative Commons
Mohammed A. Saleh,

Ahmed El-Moghazy,

Adel Helmy Elgohary

et al.

Vaccines, Journal Year: 2025, Volume and Issue: 13(2), P. 126 - 126

Published: Jan. 27, 2025

Infectious diseases continue to pose a significant global health threat. To combat these challenges, innovative vaccine technologies are urgently needed. Nanoparticles (NPs) have unique properties and emerged as promising platform for developing next-generation vaccines. revolutionizing the field of development, offering new era immunization. They allow creation more effective, stable, easily deliverable Various types NPs, including lipid, polymeric, metal, virus-like particles, can be employed encapsulate deliver components, such mRNA or protein antigens. These NPs protect antigens from degradation, target them specific immune cells, enhance antigen presentation, leading robust durable responses. Additionally, simultaneously multiple antigens, adjuvants, in single formulation, simplifying production administration. Nanovaccines offer approach food- water-borne bacterial diseases, surpassing traditional formulations. Further research is needed address burden infections. This review highlights potential revolutionize platforms. We explore their mechanisms action, current applications, emerging trends. The discusses limitations nanovaccines, solutions role artificial intelligence effective accessible nanovaccines infectious diseases.

Language: Английский

Citations

0
Engineered Exosomes Loaded in Intrinsic Immunomodulatory Hydrogels with Promoting Angiogenesis for Programmed Therapy of Diabetic Wounds DOI
Wei‐Chien Huang,

Qianru Guo,

Hongrong Wu

et al.

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

Published: April 6, 2025

Inducing rapid angiogenesis by delivering specific biological cues is critical for diabetic wound healing. Nevertheless, the hindered inflammatory microenvironment, and immune cells fail to orchestrate responses Herein, vascular endothelial growth factor (VEGF) plasmids-loaded macrophage exosomes (Exos) were fabricated enfolded in injectable self-healing hydrogels programmed therapy of wounds through sequentially intrinsically modulating microenvironment promoting angiogenesis. The hydrogels, formed via dynamical Schiff base reactions using modified polysaccharides, regulate broad-spectrum antioxidant activity phenotype regulation, restoring tissue redox homeostasis. Furthermore, can stabilize release engineered exosomes. By integration generation VEGF Exos, secretion M2 macrophages, enhanced binding receptor 2 high affinity sulfated chitosan, intrinsic immunomodulatory effectively promote accelerate healing process.

Language: Английский

Citations

0
Cancer Nanovaccines: Mechanisms, Design Principles, and Clinical Translation DOI Creative Commons

Gabriel de Camargo Zaccariotto,

Maria Julia Bistaffa, Angelica Maria Mazuera Zapata

et al.

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

Published: April 9, 2025

Cancer immunotherapy has transformed the landscape of oncological treatment by employing various strategies to teach immune system eliminate tumors. Among these, cancer nanovaccines are an emerging strategy that utilizes nanotechnology enhance activation in response tumor antigens. This review addresses principles behind different technologies this field aimed at generating a robust and effective response. The diversity adopted for design is discussed, including types active agents, nanocarriers, their functionalizations, incorporation adjuvants. Furthermore, optimize nanoparticle formulations antigen presentation, target cells, organs promote strong durable antitumor responses explored. Finally, we analyze current state clinical application, highlighting ongoing trials future potential nanovaccines. insights presented aim guide research development efforts field, contributing advancement more targeted fight against cancer.

Language: Английский

Citations

0
Emerging Roles of ncRNAs in Type 2 Diabetes Mellitus: From Mechanisms to Drug Discovery DOI Creative Commons
Yue Yang, Hao Cheng

Biomolecules, Journal Year: 2024, Volume and Issue: 14(11), P. 1364 - 1364

Published: Oct. 27, 2024

Type 2 diabetes mellitus (T2DM), a high-incidence chronic metabolic disorder, has emerged as global health issue, where most patients need lifelong medication. Gaining insights into molecular mechanisms involved in T2DM development is expected to provide novel strategies for clinical prevention and treatment. Growing evidence validates that non-coding RNAs (ncRNAs) including microRNAs (miRNAs), long (lncRNAs), circular (circRNAs) function crucial regulators multiple biological processes of T2DM, inspiring various potential targets drug candidates. In this review, we summarize the current understanding ncRNA roles discuss use ncRNAs active molecules discovery.

Language: Английский

Citations

1