A Pleiotropic Nanomedicine Mitigates Splenic Hyperplasia, Ineffective Erythropoiesis, G6PDH Anomaly through Redox Buffering in Preclinical Mice Model.

IF 3.6 4区 医学 Q2 CHEMISTRY, MEDICINAL ChemMedChem Pub Date : 2024-11-15 DOI:10.1002/cmdc.202400698
Monojit Das, Susmita Mondal, Ria Ghosh, Lopamudra Roy, Anjan Kumar Das, Siddhartha Sankar Bhattacharya, Debasish Pal, Debasish Bhattacharya, Prantar Chakrabarti, Asim Kumar Mallick, Jayanta Kumar Kundu, Samir Kumar Pal
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Abstract

Here, we present a pleiotropic nanomedicine-a smart, functionalized redox buffering nanoparticle-that may be used to treat hematological diseases, associated splenic hyperplasia, and issues related to restricted erythropoiesis. With a diameter of 5-7 nm, the spherical nanomaterial is made of manganese oxide and citrate. Here, we have produced the novel nanomaterial and, using cutting-edge electron microscopic and spectroscopic techniques, extensively assessed its redox buffering potential in vitrowith its structural integrity. Using an appropriate animal model (phenyl hydrazine, PHz, intoxicated C57BL/6J mice), we assessed the therapeutic efficacy of the redox buffering nanomedicine in the treatment of anemia and related consequences. We have further investigated the intricate molecular mechanism of the nanomedicine and its therapeutic impact, which includes increased erythropoiesis and G6PDH production, decreased inflammatory responses, mitigation of splenic hyperplasia, and synergistic intracellular redox-buffering. To the best of our knowledge, our studies would find relevance in the innovative management of anemia, decreased erythropoiesis, and splenic hyperplasia.

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一种多效纳米药物通过氧化还原缓冲作用减轻临床前小鼠模型的脾脏增生、红细胞生成障碍和 G6PDH 异常。
在这里,我们展示了一种多效纳米药物--一种智能、功能化氧化还原缓冲纳米粒子,它可用于治疗血液病、相关的脾脏增生以及与红细胞生成受限有关的问题。这种球形纳米材料的直径为 5-7 纳米,由氧化锰和柠檬酸盐制成。在这里,我们制作了这种新型纳米材料,并利用最先进的电子显微镜和光谱技术广泛评估了其在玻璃体内的氧化还原缓冲潜力及其结构的完整性。我们利用适当的动物模型(苯肼中毒的 C57BL/6J 小鼠),评估了氧化还原缓冲纳米药物在治疗贫血及相关后果方面的疗效。我们进一步研究了该纳米药物复杂的分子机制及其治疗效果,其中包括增加红细胞生成和 G6PDH 生成、减少炎症反应、减轻脾脏增生以及协同细胞内氧化还原缓冲作用。据我们所知,我们的研究将在贫血、红细胞生成减少和脾脏增生的创新管理中发挥作用。
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来源期刊
ChemMedChem
ChemMedChem 医学-药学
CiteScore
6.70
自引率
2.90%
发文量
280
审稿时长
1 months
期刊介绍: Quality research. Outstanding publications. With an impact factor of 3.124 (2019), ChemMedChem is a top journal for research at the interface of chemistry, biology and medicine. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies. ChemMedChem publishes primary as well as critical secondary and tertiary information from authors across and for the world. Its mission is to integrate the wide and flourishing field of medicinal and pharmaceutical sciences, ranging from drug design and discovery to drug development and delivery, from molecular modeling to combinatorial chemistry, from target validation to lead generation and ADMET studies. ChemMedChem typically covers topics on small molecules, therapeutic macromolecules, peptides, peptidomimetics, and aptamers, protein-drug conjugates, nucleic acid therapies, and beginning 2017, nanomedicine, particularly 1) targeted nanodelivery, 2) theranostic nanoparticles, and 3) nanodrugs. Contents ChemMedChem publishes an attractive mixture of: Full Papers and Communications Reviews and Minireviews Patent Reviews Highlights and Concepts Book and Multimedia Reviews.
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A Pleiotropic Nanomedicine Mitigates Splenic Hyperplasia, Ineffective Erythropoiesis, G6PDH Anomaly through Redox Buffering in Preclinical Mice Model. [18F]NP3-627, a candidate PET imaging agent targeting the NLRP3 inflammasome in the central nervous system. Biocatalytic Amino Acid Functionalisation. Structure-Activity-Relationships of the Stability of six Pentathiepins towards Glutathione: Possible Correlations with Biological Activities. New Indole-based Phenylthiazolyl-2,4-dihydropyrazolones as Tubulin polymerization inhibitors: Multicomponent synthesis, cytotoxicity evaluation, and in silico studies.
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