ANALYTICAL CHEMISTRY
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2025
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IF 6.7
Hong Wang,Tong Zhu,Wanying Li,Zhangjun Hu,Xin Yang,Qiong Zhang,Peng Huang,Jiwen Hu,Zhihui Feng
As a key signaling molecule, sulfur dioxide (SO2) plays a crucial role in maintaining physiological homeostasis. In this work, we designed a mitochondria-targeted fluorescent probe (MIC) for independently detect SO2 (short-wavelength) and DNA (long-wavelength) in real time. It is worth noting that our research reveals a dual role of that SO2 in regulating oxidative stress. At appropriate levels, it acts as a modulator, whereas excessive amounts induce apoptosis by reducing mitochondrial membrane potential, upregulating p53/Bax, downregulating Bcl-2, and activating the caspase-3 cascade. The apoptotic process induces mitochondrial membrane permeability changes, triggering the release and nuclear translocation of the probe MIC, which subsequently emits red fluorescence. Using time-resolved fluorescence imaging technology, we further observed a significant increase in the average fluorescence lifetime of the DNA channel. This finding demonstrates that the MIC probe not only enables dual-channel monitoring of mitochondrial SO2 and nuclear DNA but also precisely evaluates the apoptotic process through changes in fluorescence lifetime. This innovative tool provides an important means for in-depth study of the SO2-mediated apoptotic mechanism and opens up new strategies for the diagnosis of mitochondrial-related diseases.
研究领域:
生物化学
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细胞生物学
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分子生物学
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生物物理学
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医学诊断
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
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2019
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IF 3.829
Xiaorong Zhou,Chuanpei Cao,Nan Li,Shaofei Yuan
The aim of this study is to construct a SYL3C aptamer-anchored microemulsion based on β-elemene and PTX (SYL3C/EP-MEs) for enhancement on colorectal cancer therapy. Such microemulsion is consist of encapsulated drugs (β-elemene and PTX), tumor targeting ligand (3’-end thiolated SYL3C aptamer), thiol conjugated site (maleimide-modified PEGylated 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine, mal-DOPE-PEG), pH-sensitive component (DOPE) and other necessary excipients. SYL3C/EP-MEs showed a spherical particle with an average particle size around 30 nm and a high encapsulation efficiency (>80%) for both drugs. β-elemene and PTX could be released controllably from SYL3C/EP-MEs as pH values changed. SYL3C/EP-MEs displayed a selective affinity to HT-29 cells, leading to an obvious increase in cellular uptake, cell apoptosis and cytotoxicity. In the HT-29 tumor xenograft-bearing nude mice model studies, SYL3C/EP-MEs showed an overwhelming tumor growth inhibition, the longest survival time and the lowest systemic toxicity among all the treatments. The potential mechanism of enhanced anti-cancer ability was probably associated with the induction of M1 macrophage polarization, the downregulation of mutant p53 protein and the reduction of bcl-2 protein expression. Collectively, the microemulsion codelivery of β-elemene and PTX using functionalization with SYL3C aptamer provides a novel approach for combinational colorectal cancer-targeted treatment.
研究领域:
药学
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肿瘤学
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药物递送系统
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癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2019
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IF 7.901
Lei Wang,Xiuxiu Niu,Qingling Song,Jiajia Jia,Yongwei Hao,Cuixia Zheng,Kaili Ding,Huifang Xiao,Xinxin Liu,Zhenzhong Zhang,Yun Zhang
With the in-depth research of organelles, the microenvironment characteristics of their own, such as the acid environment of lysosomes and the high temperature environment of mitochondria, could be used as a natural and powerful condition for tumor therapy. Based on this, we constructed a two-step precise targeting nanoplatform which can realize the drug release and drug action triggered by the microenvironment of lysosomes (endosomes) and mitochondria, respectively. To begin with, the mesoporous silica nanoparticles (MSNs) were modified with triphenylphosphonium (TPP) and loaded with 2,2′-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIPH). Then, folic acid (FA) targeted pH-sensitive liposomes containing docetaxel (Lipo/DTX-FA) were prepared by thin-film dispersion method, and the core-shell AIPH/ [email protected] /DTX-FA nanoparticles were constructed by self-assembly during the hydration of the liposomes. When this nanoplatform entered into the tumor cells through FA receptor-mediated endocytosis, the pH-sensitive liposomes were destabilized in the lysosomes, resulting in the release of DTX and AIPH/MSN-TPP nanoparticles. After that, AIPH was delivered to mitochondria by AIPH/MSN-TPP, and the alkyl radicals produced by AIPH under the high temperature environment can cause oxidative damage to mitochondria. Not only that, the DTX could enhance the anti-tumor effect of AIPH by downregulating the expression of anti-apoptotic Bcl-2 protein. The in vitro and in vivo results demonstrate that this delivery system could induce apoptosis based on organelles’ s own microenvironment, which provides a new approach for tumor therapy.
研究领域:
纳米技术
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肿瘤治疗
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药学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2018
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IF 7.877
Chenfeng Xu,Yu Sun,Yan Qi,Yulin Yu,Yangzhou He,Mei Hu,Qian Hu,Tingting Wu,Dan Zhang,Lihuan Shang,Huan Deng,Zhiping Zhang
Tumor heterogeneity is considered as one of main obstacles to limit the clinical application of stimuli-responsive nanocarriers . Multidrug resistance (MDR) is also a major challenge in cancer chemotherapy . Here, we developed a tumor redox heterogeneity-responsive prodrug with self-induced reactive oxygen species (ROS) amplification property for facilitating rapid drug release and overcoming MDR and lung metastasis . The prodrug can self-assemble into polymer micelles (PMs) with high drug loading content (~30%), good physiological stability, prolonged systemic circulation and enhanced tumor distribution. Moreover, the prodrug PMs can stimulate tumor-specific ROS signal amplification, which provided a replenishment of consumed ROS necessary for rapid and complete drug release. The elevated ROS could not only evoke the mitochondria-dependent apoptosis by caspase-9/3 activation, but also inhibit inherent and acquired drug resistance by altering expression of Bcl-2 protein family and by reducing mitochondria membrane potential (ΔΨm) and ATP level in cancer cells. As a result, the prodrug PMs showed enhanced efficacy for inhibiting tumor growth in S180 sarcoma tumor model and in drug-resistant tumor model MCF-7/ADR and preventing lung metastasis in 4T1 in situ breast cancer model. This novel approach reported here may provide a promising strategy in the design of stimuli-responsive nanocarriers for efficient therapy of multidrug resistant and metastatic tumor.
研究领域:
癌症治疗
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药学
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纳米技术
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生物医学工程
✓ 已验证
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）