INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Jing Lv,Guangyu Liu,Huimin Gao,Yutao He,Xiaorong Tang,Ziqi Wang,Kaikai Sun,Kulbaram Bayazitova,Zhongliang Jiang
Trehalose, as a food and feed additive, can regulate physiological and pathological processes by activating autophagy, yet the molecular mechanism of trehalose dominated a rise in autophagy has not been elucidated. This study investigated the mechanisms of trehalose-induced autophagy in porcine granulosa cells (PGCs). Trehalose was internalized into PGCs by endocytosis and caused a temporary change of the lysosome pH, ultimately inducing autophagy. Furthermore, miRNA-seq analysis of PGCs indicated that trehalose upregulated the expression of miR-221-5p_R-4, which can target nuclear receptor binding factor 2 (NRBF2) to induce autophagy of PGCs. In summary, this study reveals that miR-221-5p_R-4 targeting NRBF2 was involved in the autophagy of PGCs challenged by trehalose, which was taken up by PGCs through endocytosis.
研究领域:
分子生物学
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细胞生物学
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生殖生物学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2021
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IF 9.229
Furong Cheng,Qingqing Pan,Wenxia Gao,Yuji Pu,Kui Luo,Bin He
Mitochondrial drug delivery has attracted increasing attention in various mitochondrial dysfunction-associated disorders such as cancer owing to the important role of energy production. Herein, we report a lysosomal pH-activated mitochondrial-targeting polymer nanoparticle to overcome drug resistance by a synergy between mitochondrial delivery of doxorubicin (DOX, an anticancer drug) and erlotinib-mediated inhibition of drug efflux. The obtained nanoparticles, DE-NPs could maintain negative charge and have long blood circulation while undergoing charge reversal at lysosomal pH after internalization by cancer cells. Thereafter, the acidity-activated polycationic and hydrophobic polypeptide domains boost lysosomal escape and mitochondrial-targeting drug delivery, leading to mitochondrial dysfunction, ATP suppression, and cell apoptosis. Moreover, the suppressed ATP supply and erlotinib enabled dual inhibition of drug efflux by DOX-resistant MCF-7/ADR cells, leading to significantly augmented intracellular DOX accumulation and a synergistic anticancer effect with a 17-fold decrease of IC50 relative to DOX. In vivo antitumor study demonstrates that DE-NPs efficiently suppressed the tumor burden in MCF-7/ADR tumor-bearing mice and led to negligible toxicity. This work establishes that a combination of mitochondrial drug delivery and drug efflux inhibition could be a promising strategy for combating multidrug resistance.
研究领域:
肿瘤学
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药理学
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生物材料学
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DOI
PubMed
高影响因子
Bioactive Materials
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2021
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IF 14.593
Tong Chen,Gaorong Han,Xiang Li
The induction of oxidative species, driven by oscillating electric field (E), has recently emerged as an effective approach for tumor inhibition, so-called electrodynamic therapy (EDT). While it offers a series of advantages attracting considerable attention, the fundamental mechanism and improvement strategies for EDT approach are being endeavored extensively with the aid of new material explorations. An interesting phenomenon observed in early studies is that the on-site concentration of chloride ion is highly favored for the induction of oxidative species and the efficacy of tumor inhibition. Following this discovery ignored previously, here for the first time, fine Pt/Cu alloy nanoparticles (PtCu 3 NPs) are integrated with chloride ion transporter (CIT) for EDT-based combinational therapy. In this system, while PtCu 3 NPs induce oxidative species under an electric field, it also effectively transforms endogenous H 2 O 2 into •OH and consumes intracellular glutathione (GSH). More importantly, with the aid of CIT, PtCu 3 [email protected] NPs promote the intracellular concentration of chloride ion (Cl − ) by transporting extracellular Cl − , facilitating the generation of oxidative species considerably. Meanwhile, CIT delivered intracellularly increases lysosomal pH, leading to the disruption of cellular autophagy and weakening the treatment resistance. In consequence, significant tumor inhibition is enabled both in vitro and in vivo, due to the combination of unique characteristics offered by PtCu 3 [email protected]
研究领域:
纳米技术
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癌症治疗
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材料科学
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生物医学工程
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DOI
PubMed
高影响因子
Small
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2015
·Vol. 11
·期 21
·2543-2554
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IF 8.368
Shi-Song Han,Ze-Yong Li,Jing-Yi Zhu,Kai Han,Zheng-Yang Zeng,Wei Hong,Wen-Xin Li,Hui-Zhen Jia,Yun Liu,Ren-Xi Zhuo,Xian-Zheng Zhang
A novel dual-pH sensitive charge-reversal strategy is designed to deliver antitumor drugs targeting to tumor cells and to further promote the nuclei internalization by a stepwise response to the mildly acidic extracellular pH (≈6.5) of a tumor and endo/lysosome pH (≈5.0). Poly( l -lysine)- block –poly( l -leucine) diblock copolymer is synthesized and the lysine amino residues are amidated by 2,3-dimethylmaleic anhydride to form β-carboxylic amide, making the polypeptides self-assemble into negatively charged micelles. The amide can be hydrolyzed when exposed to the mildly acidic tumor extracellular environment, which makes the micelles switch to positively charged and they are then readily internalized by tumor cells. A nuclear targeting Tat peptide is further conjugated to the polypeptide via a click reaction. The Tat is amidated by succinyl chloride to mask its positive charge and cell-penetrating function and thus to inhibit nonspecific cellular uptake. After the nanoparticles are internalized into the more acidic intracellular endo/lysosomes, the Tat succinyl amide is hydrolyzed to reactivate the Tat nuclear targeting function, promoting nanoparticle delivery into cell nuclei. This polypeptide nanocarrier facilitates tumor targeting and nuclear delivery simultaneously by simply modifying the lysine amino residues of polylysine and Tat into two different pH-sensitive β-carboxylic amides.
研究领域:
药学
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纳米技术
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癌症治疗
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
Future Medicinal Chemistry
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2024
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IF 3.2
Haili Yang,Xiaoyang Zhang,Letian Xu,Yuting Zhou,Rui Ma,Hao Chen,Siqin Zhao,Munkhtsetseg Baatar,Lvyi Chen,Xukun Deng,Hongwei Gu,Xiaoming Wang
Aim: Lysosomal pH changes are associated with drug resistance, cell growth and invasion of tumors, but effective and specific real-time monitoring of lysosomal pH compounds for cancer therapy is lacking. Materials & methods: Here, based on the covalent linkage of the anticancer drug palbociclib and fluorescent dye fluorescein isothiocyanate (FITC), we designed and developed a novel palbociclib-derived multifunctional molecule (Pal-FITC) for lysosomal targeting and diagnostic therapeutic integration. Results & discussion: Pal-FITC fluoresces is 20-fold stronger than that of FITC and shows a linear response in the pH range of 4.0–8.2 (R2 = 0.9901). Pal-FITC blocks cells in G1 phase via Cyclin D-CDK4/6-Rb. Conclusion: Our study provides new strategies for tumor-targeted imaging and personalized therapy.
研究领域:
肿瘤学
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药物化学
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分子生物学
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诊疗一体化
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）