Oxidative Stress and Chronic Myeloid Leukemia: A Balance between ROS-Mediated Pro- and Anti-Apoptotic Effects of Tyrosine Kinase Inhibitors DOI Creative Commons
Alessandro Allegra,

Giuseppe Mirabile,

Santino Caserta

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(4), P. 461 - 461

Published: April 13, 2024

The balanced reciprocal translocation t (9; 22) (q34; q11) and the BCR-ABL fusion gene, which produce p210 bcr-abl protein production with high tyrosine kinase activity, are characteristics of chronic myeloid leukemia, a myeloproliferative neoplasm. This aberrant affects several signaling pathways connected to both apoptosis cell proliferation. It has been demonstrated that inhibitor treatment in leukemia acts by inducing oxidative stress and, depending on its level, can activate responsible for either or survival leukemic cells. Additionally, reactive oxygen species generation also mediate through genomic activation. Furthermore, it was shown role BCR-ABL-independent BCR-ABL-dependent resistance kinases, while patients were found have significantly reduced antioxidant level. ideal environment therapy is produced favorable status. We discuss latest studies aim manipulate redox system alter cancerous

Language: Английский

Metabolic Stability and Targeted Delivery of Oligonucleotides: Advancing RNA Therapeutics Beyond The Liver DOI Creative Commons

Puneet Anand,

Yu Zhang,

Suraj Patil

et al.

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

Published: Jan. 8, 2025

Oligonucleotides have emerged as a formidable new class of nucleic acid therapeutics. Fully modified oligonucleotides exhibit enhanced metabolic stability and display successful clinical applicability for targets formerly considered "undruggable". Accumulating studies show that conjugation to targeting modalities stabilized oligonucleotides, especially small interfering RNAs (siRNAs), has enabled robust delivery intended cells/tissues. However, the major challenge in field been targeted (siRNAs antisense (ASOs)) extrahepatic tissues. In this Perspective, we review chemistry innovations emerging approaches revolutionized oligonucleotide drug discovery development. We explore findings from both academia industry highlight potential indications involving different organs─including skeletal muscles, brain, lungs, skin, heart, adipose tissue, eyes. all, continued advances coupled with conjugation-based or novel administration routes will further advance

Language: Английский

Citations

2
Framework nucleic acid-based nanoparticles enhance temozolomide sensitivity in glioblastoma DOI Creative Commons
Yufei Lan,

Xiaodie Li,

Boyang Liu

et al.

Drug Resistance Updates, Journal Year: 2024, Volume and Issue: 76, P. 101122 - 101122

Published: July 27, 2024

O

Language: Английский

Citations

16
Innovative Lipid Nanoparticles Co-Delivering Hydroxychloroquine and siRNA for Enhanced Rheumatoid Arthritis Therapy DOI Creative Commons

Yanru Feng,

Xintong Pan,

Ziqian Li

et al.

Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(1), P. 45 - 45

Published: Jan. 1, 2025

Background: Rheumatoid arthritis (RA) is a debilitating autoimmune disorder characterized by chronic inflammation and joint damage. Despite advancements in treatment, complete remission remains elusive. Methods: In this study, we introduce novel lipid nanoparticle formulation co-delivering hydroxychloroquine (HCQ) siRNA targeting TNF-α (siTNF-α) using microfluidic technology, marking the first use of such combination for RA therapy. Results: LPS-stimulated RAW 264.7 cells, nanoparticles effectively reduced inflammatory markers. When administered via an intra-articular injection rat model, they significantly decreased demonstrated good biological safety. Conclusions: This pioneering approach highlights potential as dual-delivery platform enhanced treatment through targeted administration.

Language: Английский

Citations

1
Dual Approaches in Oncology: The Promise of siRNA and Chemotherapy Combinations in Cancer Therapies DOI Creative Commons
Carolina Sousa, Mafalda Videira

Onco, Journal Year: 2025, Volume and Issue: 5(1), P. 2 - 2

Published: Jan. 2, 2025

The integration of small interfering RNA (siRNA) with traditional cancer therapies represents a promising frontier in oncology aimed at enhancing treatment effectiveness, reducing side effects, and overcoming drug resistance. This review highlights the potential siRNA to selectively silence genes that are overexpressed or uniquely expressed cells, thereby disrupting critical pathways support tumor growth survival. Key target discussed include survivin, VEGF, EGFR, c-MET, HER2, MUC1, Bcl-2, all which play vital roles proliferation, angiogenesis, resistance therapies. Clinical trials investigating various candidates, such as EZN-3042 ALN-VSP, indicate these generally well-tolerated; however, significant challenges persist, including effective delivery stability siRNA. Recent advancements nanoparticle-based systems have shown promise addressing issues. Future research will focus on optimizing methods, personalizing based individual genetic profiles, establishing clearer regulatory guidelines for approval. As field evolves, siRNA-based combination poised become an integral part precision oncology, offering new therapeutic options hope patients difficult-to-treat cancers.

Language: Английский

Citations

1
DNA origami-based composite nanosandwich for iteratively potentiated chemo-immunotherapy DOI
Mengyue Li, Hanxi Zhang,

Peizheng Xiong

et al.

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: 379, P. 452 - 465

Published: Jan. 17, 2025

Language: Английский

Citations

1
Clinical Applications of Targeted Nanomaterials DOI Creative Commons

Ankesh Kumar,

SK Shahvej,

Pankaj Yadav

et al.

Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(3), P. 379 - 379

Published: March 17, 2025

Targeted nanomaterials are at the forefront of advancements in nanomedicine due to their unique and versatile properties. These include nanoscale size, shape, surface chemistry, mechanical flexibility, fluorescence, optical behavior, magnetic electronic characteristics, as well biocompatibility biodegradability. attributes enable application across diverse fields, including drug delivery. This review explores fundamental characteristics emphasizes importance clinical applications. It further delves into methodologies for nanoparticle programming alongside discussions on trials case studies. We discussed some promising nanomaterials, such polymeric nanoparticles, carbon-based metallic role biomedical underscores significant translating applications highlights potential these innovative approaches revolutionizing medical field.

Language: Английский

Citations

1
In Vivo Endothelial Cell Gene Silencing by siRNA‐LNPs Tuned with Lipoamino Bundle Chemical and Ligand Targeting DOI Creative Commons

Mina Yazdi,

Jana Pöhmerer,

Morteza Hasanzadeh Kafshgari

et al.

Small, Journal Year: 2024, Volume and Issue: 20(42)

Published: June 25, 2024

Although small-interfering RNAs (siRNAs) are specific silencers for numerous disease-related genes, their clinical applications still require safe and effective means of delivery into target cells. Highly efficient lipid nanoparticles (LNPs) developed siRNA delivery, showcasing the advantages novel pH-responsive lipoamino xenopeptide (XP) carriers. These sequence-defined XPs assembled by branched lysine linkages between cationizable polar succinoyl tetraethylene pentamine (Stp) units apolar fatty acids (LAFs) at various ratios bundle or U-shape topologies. Formulation siRNA-LNPs using LAF

Language: Английский

Citations

8
Tea polyphenol nanoparticles enable targeted siRNA delivery and multi-bioactive therapy for abdominal aortic aneurysms DOI Creative Commons
Zhenhua Wu, Peng Zhang, Jie Yue

et al.

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Aug. 8, 2024

Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease, while there lack of pharmaceutical interventions to halt AAA progression presently. To address the multifaceted pathology AAA, this work develops novel multifunctional gene delivery system simultaneously deliver two siRNAs targeting MMP-2 and MMP-9. The (TPNs-siRNA), formed through oxidative polymerization self-assembly epigallocatechin gallate (EGCG), efficiently encapsulates during self-assembly. TPNs-siRNA safeguards from biological degradation, facilitates intracellular siRNA transfection, promotes lysosomal escape, releases silence Additionally, TPNs, serving as multi-bioactive material, mitigates stress inflammation, fosters M1-to-M2 repolarization macrophages, inhibits cell calcification apoptosis. In experiments with mice, accumulated persisted in aneurysmal tissue after intravenous delivery, demonstrating that can be significantly distributed macrophages VSMCs relevant pathogenesis. Leveraging carrier's intrinsic properties, targeted by TPNs exhibits synergistic effect for enhanced therapy. Furthermore, gradually metabolized excreted body, resulting excellent biocompatibility. Consequently, emerges promising nanotherapy nanocarrier effective

Language: Английский

Citations

8
Nonviral targeted mRNA delivery: principles, progresses, and challenges DOI Creative Commons
Xi He, Guohong Li, Li-Hsin Huang

et al.

MedComm, Journal Year: 2025, Volume and Issue: 6(1)

Published: Jan. 1, 2025

Abstract Messenger RNA (mRNA) therapeutics have garnered considerable attention due to their remarkable efficacy in the treatment of various diseases. The COVID‐19 mRNA vaccine and RSV been approved on market. Due inherent nuclease‐instability negative charge mRNA, delivery systems are developed protect from degradation facilitate its crossing cell membrane express functional proteins or peptides cytoplasm. However, deficiency transfection efficiency targeted biological distribution still major challenges for systems. In this review, we first described physiological barriers process then discussed design approach recent advances with an emphasis tissue/cell‐targeted abilities. Finally, pointed out existing future directions deep insights into efficient We believe that a high‐precision system can greatly improve therapeutic effects bio‐safety accelerate clinical transformations. This review may provide new direction serve as useful guide researchers who looking suitable system.

Language: Английский

Citations

0
Antibody/siRNA Nanocarriers Against Wnt Signaling Suppress Oncogenic and Stem‐Like Behavior in Triple‐Negative Breast Cancer Cells DOI Open Access
Elise C. Hoover, Emily S. Day

Journal of Biomedical Materials Research Part A, Journal Year: 2025, Volume and Issue: 113(1)

Published: Jan. 1, 2025

Triple-negative breast cancer (TNBC) is infamous for its aggressive phenotype and poorer prognosis when compared to other subtypes. One factor contributing this poor that TNBC lacks expression of the receptors available hormonal or molecular-oriented therapies attack. New treatments exploit biological targets specific are desperately needed improve patient outcomes. promising target therapeutic manipulation Wnt signaling pathway, which has been associated with many invasive cancers, including TNBC. This pathway activated in cells extracellular ligands bind overexpressed Frizzled7 (FZD7) transmembrane receptors, leading downstream activation intracellular β-catenin proteins. To inhibit cells, polymer nanoparticles (NPs) modified anti-FZD7 antibodies small interfering RNAs (siRNAs) were developed, their impact on oncogenic behavior treated was investigated. When control NPs, Wnt-targeted NPs induced greater levels oncogene suppression. led inhibition stem-like properties, cell proliferation, drug resistance, spheroid formation capacity. work demonstrates a approach targeting counter cellular phenotypes drive disease progression.

Language: Английский

Citations

0