BIOSENSORS & BIOELECTRONICS
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2017
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IF 7.78
Yiyi Tao,Dan Yin,Mingchao Jin,Jie Fang,Tao Dai,Yi Li,Yuxia Li,Qinli Pu,Guoming Xie
An electrochemical microRNA (miRNA) analysis platform by combining double-loop hairpin probe (DHP) and doxorubicin-loaded gold nanoparticles ( [email protected] ) for ultrasensitive miRNA detection is proposed. Firstly, we here report a DHP that is simultaneously engineered to incorporate a miRNA recognition sequence, an output segment and output's complementary fragment. The important aspect of this hairpin probe is that it would not be degraded by duplex specific nuclease (DSN) and circumvents elaborately chemical modification disadvantages encountered by classic molecular beacon . For the DHP-based DSN signal amplification system, DHP hybridizes with target miRNA to form DNA-miRNA heteroduplexes , and the DSN can hydrolyze the DNA in the heteroduplexes structure selectively, while released target miRNA strand can initiate another cycle resulting in a significant signal amplification and the accumulated output segments could be responsible for strand displacement on the electrode directly. Furthermore, a great deal of doxorubicin (Dox) are loaded on the gold nanoparticles (AuNPs) to fabricate the [email protected] biocomposites that could magnify the electrochemical signal and enable the ultrasensitive analysis of miRNA. As a result, the miRNA was capable of being detected in a limit of 0.17 pM and other kinds of miRNA were discriminated facilely by this method. The described DHP as a toolbox and the nano-biocomposites as a novel signal material would not only promote the design of electrochemical biosensors but also open a good way to promote the establishment of test method in malignant tumors.
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JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE
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2013
·Vol. 25
·期 3
·723-731
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IF 2.141
Shi Zhonggen,Guo Rui,Li Weichang,Zhang Yi,Xue Wei,Tang Yu,Zhang Yuanming
Chitosan (CS) was first modified hydrophobically with deoxycholic acid (DCA) and then with polyethylene glycol (PEG) to obtain a novel amphiphilic polymer (CS–DCA–PEG). This was covalently bound to folic acid (FA) to develop nanoparticles (CS–DCA–PEG–FA) with tumor cell targeting property. The structure of the conjugates was characterised using Fourier transform infrared and 1 H nuclear magnetic resonance spectroscopy and X-ray diffraction. Based on self-aggregation, the conjugates formed nanoparticles with a low critical aggregation concentration of 0.035 mg/ml. The anti-cancer drug doxorubicin (DOX) was encapsulated into the nanoparticles with a drug-loading capacity of 30.2 wt%. The mean diameter of the DOX-loaded nanoparticles was about 200 nm, with a narrow size distribution. Transmission electron microscopy images showed that the DOX-loaded nanoparticles were spherical. The drug release was studied under different conditions. Furthermore, the cytotoxic activities of DOX in CS–DCA–PEG–FA nanoparticles against folate receptor (FR)-positive HeLa cells and FR-negative fibroblast 3T3 cells were evaluated. These results suggested that the CS–DCA–PEG–FA nanoparticles may be a promising vehicle for the targeting anticancer drug to tumor cells.
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INTERNATIONAL IMMUNOPHARMACOLOGY
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2025
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IF 4.7
Xinyi Li,Hui Song,Yiwen Yuan,Na Jiang,Wei Duan,Tianzhao Xu,Chang Liu,Xinghui Liu
Cardiovascular diseases have long posed a significant threat to public health. Among them, myocarditis is a major category of cardiovascular disorders that is characterized by high mortality during its acute phase, necessitating urgent medical attention. This study aims to explore the therapeutic effects and underlying mechanisms of Spi1-mediated gene regulation in chemotherapy induced cardiomyopathy. To validate our findings, we employed bioinformatics analysis methods and established myocarditis models using the chemotherapeutic drug doxorubicin in both cellular and animal models. Our results demonstrated that the inhibition of Spi1 significantly suppressed inflammatory factor expression in H9C2 rat cardiomyocytes. Furthermore, in C57BL/6 mouse model, Spi1 inhibition was shown to improve cardiac function and alleviate both myocardial inflammation and fibrosis in mice with doxorubicin-induced myocarditis. Mechanistic investigations revealed that Spi1 suppression altered the expression of genes associated with immune response, cell differentiation and proliferation. Notably, Spi1 modulates the expression of YTHDF2, thereby influencing the PI3K/AKT/mTOR signaling pathway and subsequently regulating the inflammatory response. Collectively, these findings suggest that Spi1 plays a pivotal role in doxorubicin-induced myocarditis by mitigating inflammatory responses and myocardial injury through the regulation of YTHDF2 and the PI3K/AKT/mTOR signaling pathways, offering a promising therapeutic target for the treatment of myocarditis.
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DRUG DELIVERY
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2025
·
IF 8.1
Yang Wang,Yanan Fu,Meiying Wu,Haoqiang Wan,Xinchun Chen,Lanlan Ge,Chenyan Shi,Yangfan Li,Xiaobin Zeng,Tianqi Wang
The chemotherapeutic drug doxorubicin (DOX) has been demonstrated to trigger pyroptosis in tumor cells at exceptionally high concentrations. Nevertheless, the administration of DOX at suprapharmacological doses could cause acute off-target cytotoxicity and severe adverse effects. Herein, a biflavonoid derivative, F24, was found to improve the sensitivity of hepatocellular carcinoma (HCC) cells to low-dose DOX and reduce the adverse effects of DOX. We demonstrated that F24 synergized with low-dose DOX to increase pyroptosis and autophagy in HCC cells through dual-target CDK6 inhibition/p53 activation at a proper ratio. To achieve this synergistic effect, nanodiscs with large hydrophobic cavities were selected to codeliver the low-dose hydrophobic drugs DOX and F24 (DOX-F24@Nanodisc, DF@N), which improved the tumor accumulation of the two drugs and ensured precise drug ratio integrity within the tumor cells. DF@N can trigger gasdermin-E (GSDME)-based pyroptosis in tumor cells, accompanied by the cleavage of caspase-3. Strikingly, knocking out GSDME or caspase-3 redirected DF@N-driven cellular death from the pyroptosis pathway to the apoptotic pathway. Furthermore, DF@N administration suppressed tumor growth and activated pyroptosis in a Huh7 mouse xenograft tumor model. Overall, F24 was found to induce autophagy by targeting CDK6 and had a synergistic effect on DOX-induced pyroptosis. These results indicate that the pyroptosis-induced DF@N nanodisc system provides an effective and secure therapeutic strategy for treating HCC.
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LANGMUIR
·
2025
·
IF 3.9
Haiqian Zhao,Fang Chen,Minghong Feng,Wenjing Lin,Hangbo Yue,Jianwei Guo,Chufen Yang
To improve the stability and drug-controlled release capability of folic acid-modified pH-responsive polymeric mixed micelles FA-PEG-PHEMA-PDEAEMA (FA-P1)/PCL-PHEMA-PPEGMA (P2), the hydroxyl termini of the PHEMA blocks in polymers FA-P1 and P2 were esterified with selenooctanoic acid (SA) to produce FA-P1-SA and P2-SA, which were capable of self-cross-linking and exhibited reduction responsiveness. Thus, folic acid-modified dual-responsive diselenide-containing mixed cross-linked micelles composed of FA-P1-SA and P2-SA were constructed and employed for the delivery of doxorubicin (DOX). Structural characterization by 1H NMR, FT-IR, Raman spectroscopy, and GPC confirmed successful SA conjugation at an esterification degree of approximately 70%. Experimental and dissipative particle dynamics (DPD) analyses showed that the DOX loading content and encapsulation efficiency of the FA-containing mixed cross-linked micelles (MCLM@DOX) (1:1 mass ratio of FA-P1-SA/P2-SA) were slightly lower than those of non-cross-linked micelles (MMSA@DOX), yet afforded superior retention under physiological conditions (16.11% vs 22.49% release at 120 h) and rapid, stimuli-triggered release (75.20% vs 83.32%) in reductive, acidic conditions. Cytotoxicity assays indicated minimal polymer toxicity after SA modification. Furthermore, FA-containing MCLM@DOX exhibited relatively good tumor-targeting and anticancer efficacy compared with FA-free counterparts (MCLM1@DOX).
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BIOMEDICAL AND ENVIRONMENTAL SCIENCES
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2025
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IF 4.1
Hao Wu,Huangshui Ma,Xinghan Wu,Qiang Sun,Lin Feng,Ruifang Jiang,Yanhong Li,Quan Shi
Objective Cancer remains a significant global health challenge, necessitating the development of effective treatment approaches. Developing synergistic therapy can provide a highly promising strategy for anti-cancer treatment through combining the benefits of various mechanisms. Methods In this study, we developed a synergistic strategy for chemo-photothermal therapy by constructing nanocomposites using gold nanorods (GNRs) and tetrahedral framework nucleic acids (tFNA) loaded with the anti-tumor drug doxorubicin (DOX). Results Our in vitro studies have systematically clarified the anti-cancer behaviors of tFNA-DOX@GNR nanocomposites, characterized by their enhanced cellular uptake and proficient lysosomal escape capabilities. It was found that the key role of tFNA-DOX@GNR nanocomposites in tumor ablation is primarily due to their capacity to induce cytotoxicity in tumor cells via a photothermal effect, which generates instantaneous high temperatures. This mechanism introduces various responses in tumor cells, facilitated by the thermal effect and the integrated chemotherapeutic action of DOX. These reactions include the induction of endoplasmic reticulum stress, characterized by elevated reactive oxygen species levels, the promotion of apoptotic cell death, and the suppression of tumor cell proliferation. Conclusion This work exhibits the potential of synergistic therapy utilizing nanocomposites for cancer treatment and offers a promising avenue for future therapeutic strategies.
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NEW JOURNAL OF CHEMISTRY
·
2022
·Vol. 46
·期 48
·23039-23049
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IF 3.925
Yongchang Ouyang,Miao Liang,Fangzhen Wang,Songqing Mei,Guangquan Mo
Herein, supported by the attractive structure of zeolitic imidazolate frameworks (ZIFs), novel porous thorny carbon dodecahedron implanted with hollow cobalt oxide nanospheres (PCD-HC) was prepared by the two-step pyrolysis of ZIFs. Morphology and structure investigations showed that PCD-HC was a highly porous rhombic dodecahedron embedded with hollow nanospheres. Elemental mapping revealed that the main dodecahedral structure of PCD-HC was a carbonized framework doped with N species. Besides, well-defined hollow Co3O4 nanospheres with abundant O vacancies were implanted. Due to the highly porous structure, embedded active species, and graphite-like structure, PCD-HC displayed distinguished electrocatalysis towards doxorubicin (DOX) with a pair of highly symmetric redox peaks and fast direct electron transfer of anthracycline. The direct electrochemistry and catalytic mechanism of the DOX redox reaction at PCD-HC were elucidated, and a PCD-HC based electrochemical sensor was developed for the DOX sensing with a broad linear range from 1.0 nM to 1.0 μM. The limit of detection was obtained as 0.15 nM (S/N = 3). Besides, PCD-HC sensor also displayed a wide detection range at a high concentration from 2.0 to 12.0 μM. Moreover, PCD-HC sensor presented a high selectivity with strong anti-interference capability towards common inorganic ions and small biomolecules. The reproducibility, repeatability, and stability were examined with satisfactory results. Significantly, a PCD-HC sensor was applied in the monitoring of DOX in HeLa cells inhibiting process, indicating a substantial detection platform for DOX sensing.
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DRUG DEVELOPMENT RESEARCH
·
2021
·Vol. 83
·期 3
·646-658
·
IF 4.36
Xinxin Cui,Kunda Du,Xiaoyin Yuan,Wen Xiao,Yayu Tao,Defeng Xu,Hang Hu
In this work, five Man-DOX conjugates with different linkers were developed for targeted DOX delivery. The five Man-DOX conjugates with different linkers were characterized by 1 H NMR, HRMS, HPLC, UV–vis, and fluorescence spectroscopy. Man-Suc-DOX, Man-TDG-DOX, and Man-DG-DOX can self-assemble into near-spherical nanoparticles with hydrodynamic diameters of 150–200 nm and negative zeta potentials in deionized water, whereas Man-SS-DOX and Man-SeSe-DOX are hardly dispersed in deionized water. The self-assembly behaviors of Man-Suc-DOX, Man-TDG-DOX, and Man-DG-DOX were studied by dissipative particle dynamics simulation and the results show that Man-Suc-DOX, Man-TDG-DOX, and Man-DG-DOX all self-assemble into spherical particles with Man and linkers on the surfaces and DOX in the interiors. The in vitro drug release study shows that Man-Suc-DOX, Man-TDG-DOX, and Man-DG-DOX exhibit limited drug release, while Man-SS-DOX and Man-SeSe-DOX exhibit glutathione-responsive drug release. The cellular uptake study shows that Man-DG-DOX exhibits the highest cellular uptake amount on HepG2 cells. Finally, Man-DG-DOX exhibits the best in vitro antitumor effect against HepG2 cells among the five Man-DOX conjugates with different linkers. Although the in vitro antitumor activity of Man-DG-DOX is still lower than free DOX, Man-DG-DOX shows significant selectivity toward HepG2 cells. Man-DG-DOX might achieve selective DOX delivery for mannose receptor overexpressed tumors.
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REACTIVE & FUNCTIONAL POLYMERS
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2022
·
IF 4.966
Guoguang Chen,Qiqi Zheng,Jie Dai,Jia Liu,Jun Yin,Xiaoqing Xu,Aiping Chen,Lili Ren
Currently, the drawbacks of the chemotherapy drugs are still demonstrated poor water solubility, systemic toxicity and even multidrug resistance (MDR) in clinical applications. To address these problems, an amphiphilic block polymer self-assembled reduction sensitive micelle , mPEG-SS-PzLL/TPGS/DOX, was synthesized for efficient anticancer therapy. The polymer had a biodegradable backbone and disulfide bond can be cleaved by reduced glutathione (GHS) in tumor cells, which led to fast release of the DOX . TPGS was designed for an increaseing drug accumulation and a reduction in drug efflux. In follow-up research, we found that mPEG-SS-PzLL/TPGS/DOX micelles achieved a high encapsulation efficiency of 96.1%. Photomicrographs gotten by TEM showed homogeneous and spherical-shaped particles with the particl size of 83.7 ± 3.2 nm. The in vitro release in high reducing conditions reached 96% within 48 h. Furthermore, the mPEG-SS-PzLL/TPGS/DOX micelles caused stronger cytotoxicity to 4 T1 cells and promising therapeutic efficacy for BALB/c mice bearing 4 T1 tumors. Therefore, an excellent drug delivery system was created by combing restore sensitivity with multidrug resistance strategy while maximize drug accumulation in tumor cells. Alternatively, this study offers a bright perspective for cancer therapy with chemotherapeutics.
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Advanced Science
·
2025
·
IF 14.1
Jiaxin Huang,Jieru Yang,Yuanying Yang,Xiaofeng Lu,Juan Xu,Shan Lu,Hong Pan,Wenhu Zhou,Wenqun Li,Songwen Chen
Doxorubicin (Dox) is a potent chemotherapeutic agent commonly used in cancer treatment. However, cardiotoxicity severely limited its clinical application. To address this challenge, a novel self-assembled nanomedicine platform, PMDDH, is developed for the co-delivery of Dox and metformin, an antidiabetic drug with cardioprotective and anti-tumor properties. PMDDH integrates metformin into a polyethyleneimine-based bioactive excipient (PMet), with Dox intercalated into double-stranded DNA and a hyaluronic acid (HA) coating to enhance tumor targeting. The PMDDH significantly improves the pharmacokinetics and tumor-targeting capabilities of Dox, while metformin enhances the drug's anti-tumor activity by downregulating programmed cell death ligand 1 (PD-L1) and activating the AMP-activated protein kinase (AMPK) signaling pathway. Additionally, the DNA component stimulates the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, which synergizes with Dox-induced immunogenic cell death (ICD) to promote a robust anti-tumor immune response. PMDDH markedly reduces Dox-induced cardiotoxicity by preserving mitochondrial function, reducing reactive oxygen species (ROS) production, and inducing protective autophagy in cardiomyocytes. These findings position PMDDH as a promising dual-function nanomedicine that enhances the anti-tumor efficacy of Dox while minimizing its systemic toxicity, offering a safer and more effective alternative for cancer therapy.
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EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS
·
2013
·Vol. 39
·期 4
·301-310
·
IF 0.944
Xu Jinhui,Sheng Yuan,Xu Feifei,Yu Ying,Chen Yun
The extended use of doxorubicin (DOX) could be limited due to the emergence of drug resistance and cardiotoxicity associated with its treatment. Conjugates of DOX with transferrin (DOX–TRF) can effectively alleviate these side effects, thereby leading to a better treatment. The effectiveness of DOX–TRF could result from the enhancement of transferrin receptor (TfR)-mediated transportation. However, detailed TfR-mediated DOX delivery has not been fully elucidated thus far, which may rely on the quantitative subcellular study of DOX distribution and metabolism. In this study, an immunoisolation assay was developed to isolate the organelles with high purity, yield and integrity. Using this immunoisolation assay together with liquid chromatography–tandem mass spectrometry (LC/MS/MS), the subcellular distribution profiles of DOX and its main metabolite doxorubicinol (DOXol) in human breast cancer cells MCF-7/WT and MCF-7/ADR were determined and compared after the treatment of DOX and DOX–TRF. As expected, DOX–TRF treated cells have a higher drug accumulation compared to DOX treated cells. DOX–TRF was predominantly cytoplasmic. In addition, TfR-mediated transportation had a significant impact on the transformation of DOX to DOXol in the cells. This study provided the evidence that immunoisolation together with LC/MS/MS is an effective technique in subcellular investigations.
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Acta Biomaterialia
·
2022
·
IF 10.633
Yang Wang,Yunfei Yi,Jie Yao,Haoqiang Wan,Mian Yu,Lanlan Ge,Xiaobin Zeng,Meiying Wu,Lin Mei
Doxorubicin (DOX) widely used in hepatocellular carcinoma (HCC) can induce serious side effects and drug resistance. Herein, we aimed to seek a strategy to improve the efficacy and reduce the side effects of DOX in HCC based on an autophagy inducer drug called isoginkgetin (ISO). The design of multifunctional nanocarriers based on hyaluronic acid-conjugated and manganese-doped mesoporous silica nanoparticles (HM) for the co-delivery of antitumor drugs against HCC provided an effective and promising antitumor strategy. Our results showed that [email protected] @DOX could efficiently inhibit HCC cell proliferation through activating autophagy through AMPKa-ULK1 pathway. Moreover, intravenous injection of [email protected] @DOX significantly suppressed HCC tumor progression in nude mouse HCC model. Collectively, our findings revealed an anti-HCC mechanism of [email protected] @DOX through autophagy and provide an effective therapeutic strategy for HCC. Statement of significance In our study, we constructed a co-delivery system by loading ISO and DOX in the mesoporous channels of manganese-doped mesoporous silica nanoparticles, which could be further conjugated with hyaluronic acid to obtain [email protected] @DOX. The nanocarriers had been demonstrated to be biodegradable under the acidic and reducing tumor microenvironment, as well as to possess the tumor targeting capability via the conjugated hyaluronic acid. In addition, [email protected] @DOX enhanced the therapeutic efficacy against human HCC tumor through the combinatorial therapies of chemotherapeutics, Mn 2+ -mediated chemodynamic therapeutics and autophagic cell death, which might be achieved through AMPK-ULK1 signaling. This work revealed that such a nanomedicine exhibited superior tumor accumulation and antitumor efficiency against HCC with extremely low systemic toxicity in an autophagy-boosted manner.
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