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Lysosomal escaped protein nanocarriers for nuclear-targeted siRNA delivery
Anal Bioanal Chem. 2021 Mar 26. doi: 10.1007/s00216-021-03297-5. Online ahead of print.ABSTRACTIn the process of drug carrier design, lysosome degradation in cells is often neglected, which makes a considerable number of drugs not play a role. Here, we have constructed a tumor treatment platform (Apn/siRNA/NLS/HA/Apt) with unique lysosomal escape function and excellent cancer treatment effect. Apoferritin (Apn) has attracted more and more attention because of its high uniformity, modifiability, and controllability. Meanwhile, its endogenous nature can avoid the risk of immune response being eliminated. We used aptamer modi...
Source: Analytical and Bioanalytical Chemistry - March 26, 2021 Category: Chemistry Authors: Xiuping Cao Xinxin Shang Yingshu Guo Xiaofei Zheng Wenxin Li Di Wu Li Sun Shanliang Mu Chuanen Guo Source Type: research

Iron-siRNA Nanohybrids for Enhanced Chemodynamic Therapy via Ferritin Heavy Chain Downregulation
Angew Chem Int Ed Engl. 2023 Mar 23:e202302255. doi: 10.1002/anie.202302255. Online ahead of print.ABSTRACTFerrous iron (Fe2+) has more potent hydroxyl radical (•OH)-generating ability than other Fenton-type metal ions, making Fe-based nanomaterials attractive for chemodynamic therapy (CDT). However, because Fe2+ can be converted by ferritin heavy chain (FHC) to nontoxic ferric form and then sequestered in ferritin, therapeutic outcomes of Fe-mediated CDT agents are still far from satisfactory. Here we report the synthesis of siRNA-embedded Fe0 nanoparticles (Fe0-siRNA NPs) for self-reinforcing CDT via FHC downregulation...
Source: Angewandte Chemie - March 23, 2023 Category: Chemistry Authors: Jun Wang Hongye Ding Yang Zhu Yina Liu Meili Yu Huilan Cai Rujiang Ao Hongwei Huang Peng Gong Yaxin Liao Zhaolin Chen Lisen Lin Xiaoyuan Chen Huanghao Yang Source Type: research

Engineering Multifunctional RNAi Nanomedicine to Concurrently Target Cancer Hallmarks for Combinatorial Therapy.
Abstract Cancer hallmarks have been providing a logical framework for understanding the complexity and heterogeneity of tumor biology, leading to the discovery of various promising targets for cancer therapy. Herein, we report a novel amorphous iron oxide nanoparticle (NP)-based RNAi strategy to co-target two cancer hallmarks. The NP technology can modulate the glycolysis pathway by silencing MCT4 to induce tumor cell acidosis, and concurrently exacerbate oxidative stress in tumor cells via the Fenton-like reaction. Our platform shows following appealing features for systemic siRNA delivery: (i) siRNA is encapsula...
Source: Angewandte Chemie - December 24, 2017 Category: Chemistry Authors: Liu Y, Ji X, Tong W, Askhatova D, Yang T, Cheng H, Wang Y, Shi J Tags: Angew Chem Int Ed Engl Source Type: research

Catecholamines Regulate Iron Homeostasis Metabolism
This study reveals epinephrine and norepinephrine as novel regulators of cellular iron homeostasis.
Source: Journal of Biological Chemistry - March 20, 2015 Category: Chemistry Authors: Tapryal, N., Vivek G, V., Mukhopadhyay, C. K. Tags: Gene Regulation Source Type: research

Acute loss of iron-sulfur clusters results in metabolic reprogramming and generation of lipid droplets in mammalian cells Cell Biology
Iron–sulfur (Fe-S) clusters are ancient cofactors in cells and participate in diverse biochemical functions, including electron transfer and enzymatic catalysis. Although cell lines derived from individuals carrying mutations in the Fe-S cluster biogenesis pathway or siRNA-mediated knockdown of the Fe-S assembly components provide excellent models for investigating Fe-S cluster formation in mammalian cells, these experimental strategies focus on the consequences of prolonged impairment of Fe-S assembly. Here, we constructed and expressed dominant–negative variants of the primary Fe-S biogenesis scaffold protein iron–...
Source: Journal of Biological Chemistry - May 25, 2018 Category: Chemistry Authors: Daniel R. Crooks, Nunziata Maio, Andrew N. Lane, Michal Jarnik, Richard M. Higashi, Ronald G. Haller, Ye Yang, Teresa W-M. Fan, W. Marston Linehan, Tracey A. Rouault Tags: Editors ' Picks Source Type: research

SMAD family member 3 (SMAD3) and SMAD4 repress HIF2{alpha}-dependent iron-regulatory genes Metabolism
Hypoxia-inducible factor 2α (HIF2α) directly regulates a battery of genes essential for intestinal iron absorption. Interestingly, iron deficiency and overload disorders do not result in increased intestinal expression of glycolytic or angiogenic HIF2α target genes. Similarly, inflammatory and tumor foci can induce a distinct subset of HIF2α target genes in vivo. These observations indicate that different stimuli activate distinct subsets of HIF2α target genes via mechanisms that remain unclear. Here, we conducted a high-throughput siRNA-based screen to identify genes that regulate HIF2α's transcriptional activity on...
Source: Journal of Biological Chemistry - March 14, 2019 Category: Chemistry Authors: Xiaoya Ma, Nupur K. Das, Cristina Castillo, Ayla Gourani, Ansu O. Perekatt, Michael P. Verzi, Yatrik M. Shah Tags: Gene Regulation Source Type: research