Angew Chem Int Ed Engl
MOE Key Laboratory for Analytical Science of Food Safety and Biology, Engineering Technology Research Center on Reagent and Instrument for Rapid Detection of Product Quality and Food Safety in Fujian Province, College of Chemistry, Fuzhou University, 350108, Fuzhou, China.
Published: May 2023
Ferrous iron (Fe ) 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 Fe 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 Fe nanoparticles (Fe -siRNA NPs) for self-reinforcing CDT via FHC downregulation. Upon internalization by cancer cells, pH-responsive Fe -siRNA NPs are degraded to release Fe and FHC siRNA in acidic endo/lysosomes with the aid of oxygen (O ). The accompanied O depletion causes an intracellular pH decrease, which further promotes the degradation of Fe -siRNA NPs. In addition to initiating chemodynamic process, Fe -catalyzed ⋅OH generation facilitates endo/lysosomal escape of siRNA by disrupting the membranes, enabling FHC downregulation-enhanced CDT.
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http://dx.doi.org/10.1002/anie.202302255 | DOI Listing |
ACS Nano
January 2025
Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China.
For idiopathic pulmonary fibrosis (IPF), interleukin 11 (IL-11) is a pivotal cytokine that stimulates the transformation of fibroblasts into myofibroblasts, thus accelerating the progression of pulmonary fibrosis. Here, we develop an innovative inhalable small interfering RNA (siRNA) delivery system termed PEI-GBZA, which demonstrates impressive efficiency in loading siIL-11 targeting IL-11 (siIL-11) and substantially suppresses the differentiation of fibroblasts into myofibroblasts and epithelial-mesenchymal transition (EMT), reduces neutrophil and macrophage recruitment, and ultimately relieves the established fibrotic lesions in the IPF model. PEI-GBZA is prepared by modifying low-molecular-weight polyethylenimine (PEI) with 4-guanidinobenzoic acid (GBZA).
View Article and Find Full Text PDFJ Nanobiotechnology
January 2025
Department of Laboratory, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710032, China.
Background: Cardiac fibrosis plays a critical role in the progression of various forms of heart disease, significantly increasing the risk of sudden cardiac death. However, currently, there are no therapeutic strategies available to prevent the onset of cardiac fibrosis.
Methods And Results: Here, biomimetic ATP-responsive nanozymes based on genetically engineered cell membranes are adapted to specifically recognize activated cardiac fibroblasts (CFs) for the treatment of cardiac fibrosis.
J Biomed Mater Res A
January 2025
Department of Biomedical Engineering, University of Delaware, Newark, Delaware, USA.
Triple-negative breast cancer (TNBC) is infamous for its aggressive phenotype and poorer prognosis when compared to other breast cancer subtypes. One factor contributing to this poor prognosis is that TNBC lacks expression of the receptors that available hormonal or molecular-oriented therapies attack. New treatments that exploit biological targets specific to TNBC are desperately needed to improve patient outcomes.
View Article and Find Full Text PDFInt J Biol Macromol
December 2024
Research Institute for Prevention of Non-Communicable Diseases, Cellular and Molecular Research Center, Qazvin University of Medical Sciences, Qazvin, Iran. Electronic address:
Integrin αvβ3, a primary cell-adhesion receptor, plays a crucial role in various biological processes, including angiogenesis, pathological neovascularization, and tumor metastasis. Its expression increases during tumor angiogenesis. The insulin-like growth factor 1 receptor (IGF1R) is a transmembrane protein that stimulates vital signaling pathways, promoting cancer cell growth, survival, and metabolism.
View Article and Find Full Text PDFACS Appl Bio Mater
December 2024
Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, 47500 Subang Jaya, Selangor, Malaysia.
Naked siRNAs are sensitive to enzymatic degradation, phagocytic entrapment, quick renal excretion, membrane impermeability, endosomal escape, and off-target effects. Designing a safe and efficient nanocarrier for siRNA delivery to the target site without toxicity remains a significant hurdle in gene therapy. CA is a unique derivative of hydroxyapatite and a highly pH-sensitive nanocarrier with strong particle aggregation and a high polydispersity index.
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