Emergence of Small Nucleic Acids as Drugs in Precision Medicine

Clinical Pharmacology & Therapeutics, Journal Year: 2025, Volume and Issue: unknown

Published: April 14, 2025

Small nucleic acid drugs including antisense oligonucleotides, small interfering RNAs, microRNAs, and aptamers, among others, have revolutionized the pharmaceutical industry in 21st century, offering novel therapeutic strategies for a myriad of diseases through precise gene expression regulation or protein synthesis modulation. As December 2024, 19 been approved globally, with applications primarily treating rare hereditary conditions, metabolic diseases, ophthalmological disorders, demonstrating great clinical potential. This review provides an overview classification, mechanism action, technical challenges, addressing drugs, focus on indications market‐available aiming to equip healthcare professionals thorough understanding practical guidance their utilization.

Language: Английский

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GSH-Responsive Heterodimeric Dual-Targeted Nanomedicine Modulates EMT to Conquer Paclitaxel-Induced Invasive Breast Cancer Metastasis

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

Published: April 15, 2025

Paclitaxel (PTX), although effective against primary breast cancer, presents formidable clinical challenges due to severe toxicity and pro-metastatic potential, a critical concern as distant metastasis causes 90% of cancer-related deaths. To address these limitations, we designed prepared tumor microenvironment-responsive nanoprodrug, PTX-SS-3'HPT@RGD-HA NPs, that engineered RGD peptide-modified hyaluronic acid (HA) nanocarriers encapsulating the antimetastatic 3'-hydroxy pterostilbene (3'HPT) PTX heterodimer linked by glutathione (GSH)-cleavable disulfide bond. These nanoparticles targeting CD44 αvβ receptors overexpressed in aggressive cancer cells synergized enhanced permeability retention effects with receptor-mediated endocytosis, facilitating superior tumor-specific drug deposition GSH-activated payload release vitro vivo. Moreover, NPs achieved excellent growth inhibition while mitigating systemic metastatic risks 4T1 tumor-bearing mice. Mechanistically, 3'HPT counteracted PTX-induced epithelial-mesenchymal transition downregulating MMP-9/N-cadherin restoring E-cadherin expression, thereby neutralizing PTX-triggered effects. This study pioneers dual-targeted, toxicity-shielding nanoplatform simultaneously improves therapeutic efficacy addresses chemotherapy-driven metastasis, offering revolutionary strategy for managing highly invasive cancer.

Language: Английский

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Integrated metabolite profiling and transcriptome analysis identify candidate genes involved in diterpenoid alkaloid biosynthesis in Aconitum pendulum

Frontiers in Plant Science, Journal Year: 2025, Volume and Issue: 16

Published: March 24, 2025

Introduction Aconitum pendulum is a well-known Tibetan medicine that possesses abundant diterpenoid alkaloids (DAs) with high medicinal value. However, due to the complicated structures of DAs and associated challenges in vitro synthesis presents, plants like remain primary source for DAs. Methods Given underutilization A. , thorough metabolomic transcriptomic analysis was conducted on its flowers, leaves, stems elucidate regulatory network underlying DA biosynthesis. Results Metabolomic profiling (utilizing UPLC-QQQ-MS/MS) identified 198 alkaloids, which 61 were relative abundance different among tissues. Without reference genome, we performed de novo assembly transcriptome . We generated 181,422 unigenes, 411 candidate enzyme genes related pathway identified, including 34 differentially expressed (DEGs). Through joint metabolome data, found correlation between detected metabolite levels various tissues expression genes. Specifically, it ApCYP1, ApCYP72, ApCYP256 may be turupellin accumulation, while ApBAHD9, ApBAHD10, ApBAHD12 positively accumulation aconitine. Furthermore, our study also revealed involved diterpene skeleton tend highly whereas their subsequent modifications are more likely leaf stem Functional gene families 77 BAHD acyltransferases, 12 O -methyltransferases, 270 CYP450 potentially biosynthesis The co-expression metabolites 116 significant correlations involving 30 58 Discussion This provides valuable resources in-depth research secondary metabolism not only deepening understanding mechanisms but providing genetic improvement metabolic engineering strategies.

Language: Английский

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Responsive ROS‐Augmented Prodrug Hybridization Nanoassemblies for Multidimensionally Synergitic Treatment of Hepatocellular Carcinoma in Cascade Assaults

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

Published: May 5, 2025

Abstract The rapid deterioration and progression of hepatocellular carcinoma (HCC) is intimately associated with copper ion overload, integrating the cuproptosis mechanism for treatment HCC presents a promising prospect. Nevertheless, cell death complexity renders efficient removal all cells insufficient solely relying on pathway. Herein, GSH‐responsive prodrug hybridization nanoassembly CA‐4S 2 @ES‐Cu exploited, which targets delivery ions to mitochondria via Elesclomol, contributing mitochondrial dysfunction evoking cuproptosis. Simultaneously, depletes GSH release CA‐4, disrupting microtubule function suppressing proliferation angiogenesis, realize dual attack against ion‐mediated metastasis HCC. Furthermore, both in mouse model synergistically elicit oxidative stress amplify effect activated immunogenetic initiate vigorous antitumor immune response cascade assault modality. Conclusively, multilevel synergistic penetrates limitations single therapy implements multidimensional targeted

Language: Английский

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