BIOMEDICAL CHROMATOGRAPHY
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2014
·Vol. 28
·期 10
·1393-1401
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IF 1.662
Bin Deng,Zhi-Ming Wang,Zi-Hao Zhou,Yi-Meng Liu,Xi-Liang Yang,Jian Song,Yu-Xiu Xiao
Cellular heterogeneity in doxorubicin (DOX) uptake and its relationship with pharmacological effect on cancer cells were quantitatively investigated for the first time. An in vitro experimental model was established by treating human leukemia K562 and breast cancer MCF-7 cells with different schedules of DOX with or without surface P-glycoprotein (P-gp) inhibitor verapamil (VER). The cellular heterogeneity in DOX uptake was quantitatively examined by single-cell analysis using capillary electrophoresis coupled with laser-induced fluorescence detection. The corresponding cytotoxic effect was tested by cellular morphology, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium and flow cytometry assays. The expression of cellular membrane surface P-gp was determined by flow cytometry. Results showed that the cellular heterogeneity exists in DOX uptake. The single-high DOX schedule leads to lower uptake heterogeneity and higher mean drug uptake. The cellular heterogeneity in DOX uptake was found to be negatively correlated with drug cytotoxicity and surface P-gp expression, with r = −0.7680 to ~ −0.9587. VER reduces the cellular variation in DOX uptake, suggesting that surface P-gp may be one of the causes of the cellular heterogeneity in DOX uptake. This research demonstrates the importance of quantitative study of cellular heterogeneity in drug uptake and its potential application in drug schedule design, response prediction and therapy modulation. Copyright © 2014 John Wiley & Sons, Ltd.
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REACTIVE & FUNCTIONAL POLYMERS
·
2014
·
IF 2.822
Juan Lv,Li Zhang,Musammir Khan,Xiangkui Ren,Jintang Guo,Yakai Feng
Nowadays, biodegradable amphiphilic block copolymers with stable performance and adjustable structure have attracted the interests of researchers in the field of drug delivery. In this work, the triblock copolymer , P(SBMD- co -PDO)- b -PEG- b -P(SBMD- co -PDO), was successfully synthesized by ring-opening polymerization of 3(S)- sec -butyl-morpholine-2,5-dione (SBMD) and p -dioxanone (PDO) with poly(ethylene glycol) (PEG) as the initiator. In phosphate buffered solution (PBS), these copolymers could self-assemble into nano-sized micelles that have a hydrophobic P(SBMD- co -PDO) core surrounded by a hydrophilic PEG shell. Because of the strong hydrogen bonding and hydrophobic interactions, doxorubicin (DOX) was loaded into the micelles with high loading capacity (LC, up to 28.4%) and encapsulation efficiency (EE, up to 62.5%). The drug-loaded micelles showed sustained-release of DOX along with the hydrolytic degradation of the micelles in PBS. Therefore, these amphiphilic triblock copolymers have potential as drug matrix for controlled release.
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ANALYTICAL AND BIOANALYTICAL CHEMISTRY
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2015
·Vol. 408
·期 3
·683-693
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IF 3.436
Chen Xing,Jiang Guimei,Wang Zhili,Hong Shanni,Zhang Yuanyuan,Guo Yahui,Cheng Hui,Wang Jine,Pei Renjun
Doxorubicin (Dox) is a DNA-targeting anthracycline antibiotic active against a wide spectrum of cancers. The interaction between Dox and double-stranded DNA (dsDNA) was used to load Dox using DNA duplexes as carriers. More importantly, the interesting DNA sequence-dependent fluorescence response of Dox could be exploited in the design of efficient Dox release systems and efficient fluorescence sensors. In this work, we demonstrated that separate introduction of G and C bases into T-rich single-stranded DNA (ssDNA) sequences afforded the best discrimination of Dox binding between dsDNA and ssDNA. For the first time, we successfully utilized this interesting DNA sequence-dependent fluorescence response of Dox as a signal transduction mechanism for the sensitive detection of biothiols in human serum. Cysteine, homocysteine, and glutathione were detected at as low as 26 nM, 37 nM, and 29 nM, respectively. The biosensors exhibited not only good selectivity, stability, and sensitivity in aqueous solutions but also a sensitive response in human serum, demonstrating their potential for diagnosis.
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Journal of Materials Chemistry B
·
2015
·Vol. 3
·期 29
·6001-6012
·
IF 4.726
Sen Lin,Fangfang Deng,Ping Huang,Lingli Li,Lei Wang,Qing Li,Ling Chen,Hao Chen,Kaihui Nan
Legumain is the only acidic asparaginly-endopeptidase in mammals that is highly up-regulated in tumor tissue and tumor associated cells. In this study, a novel legumain protease-activated micelle was successfully synthesized and prepared by loading with doxorubicin (DOX). The prepared micelle exhibited a spherical morphology and possessed a low critical micelle concentration of 1.21 × 10−3 mg mL−1 with a DOX loading capacity and entrapment efficiency of 4.05% and 60.6% respectively. The release profile of DOX from this micelle formulation was observed to be legumain concentration dependent. The micelle encapsulation of DOX highly enhanced the cellular uptake of DOX by tumor cell lines of DAOY, Y79, MCF-7, and MCF-7/DOX. Furthermore, encapsulation of DOX boosts the cytotoxicity against the tumor cells while reducing cytotoxicity against RPE and HEK293 cells. In addition, blank micelles did not exhibit any biological effects on tumor or RPE or HEK293 cells at the concentration range of 0–300 μg mL−1, indicating good biocompatibility. The results suggest that this micelle formulation has potential applications in sustained drug delivery for legumain up-regulated tumors.
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JOURNAL OF MATERIALS SCIENCE & TECHNOLOGY
·
2017
·
IF 2.764
Bei Xie,Jipeng Yi,Jian Peng,Xing Zhang,Lei Lei,Dapeng Zhao,Zhixin Lei,Hemin Nie
Co-delivery of chemical drugs and therapeutic genes for synergistic therapy provides a promising strategy to treat devastating diseases. However, the real-time coordination patterns between chemical drugs and therapeutic genes remain poorly understood. Herein, the complexes of doxorubicin/graphene oxide-polyethyleneimine/p53 plasmid (Dox/GO-PEI/p53) were fabricated and employed to investigate the synergistic manner between Dox and p53 in the inhibition of HeLa cell growth. GO was conjugated with PEI to form the GO-PEI backbone as the delivery vector. The GO backbone provided surfaces with a high specific area to load Dox via the π-π stacking interaction, and was able to release Dox significantly faster at pH 5.0 than at pH 7.0, while the positively charged PEI section of GO-PEI could condense plasmids into GO-PEI/DNA nanoparticles via the electrostatic interaction . The nanoparticles efficiently mediated the transfection of DNA in HeLa cells, with lower cytotoxicity compared to PEI/DNA nanoparticles. Furthermore, the complexes of Dox/GO-PEI/p53 released Dox and expressed p53 gene in a sequential manner, and showed successive inhibition of the in vitro growth of HeLa cells. This type of drug/GO-PEI/DNA complex can be employed as a platform to investigate the coordination pattern between chemical drugs and therapeutic genes for tumor therapy.
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SPECTROSCOPY LETTERS
·
2025
·
IF 1.6
Na Ni,Yanhua Tang,Nian Ding,Kang Peng,Xinwang Zhang,Qianqian Su
This study used the acidic anionic dye eosin Y (EY) as a resonance Rayleigh scattering (RRS) probe to develop a method for the detection of doxorubicin hydrochloride (DOX). In dilute hydrochloric acid solution medium, eosin Y interacted with each other through hydrogen bonding to form supramolecular aggregates. The addition of doxorubicin hydrochloride induced an ion-conjugation process and dissociated the hydrogen-bonded supramolecular aggregates that eosin Y had formed. As a result, the RRS signal of eosin Y at 534 nm was significantly diminished. The reaction conditions were optimized and the mechanism of RRS intensity reduction was explored. It was found that the main reason for the weakening of the RRS intensity was the decrease in particle size. The range of 0.5–5.0 mg/L is well-represented by the concentration of doxorubicin hydrochloride, which shows decent linear relationship. The linear regression equation was ΔI = 15044c + 10465 with a correlation coefficient R of 0.9995, and a limit of detection of 0.085 mg/L. The recoveries ranged from 97.33% to 102.94%. This work provided a new, sensitive, and cost-effective method for estimating doxorubicin hydrochloride, which can be successfully applied to the estimation of doxorubicin hydrochloride for injection.
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JOURNAL OF MOLECULAR LIQUIDS
·
2024
·
IF 5.3
Baoshan Tang,Fen Xiong,Lanxiang Liu,Juan Xu,Jinju Ma,Hong Zhang
As an antibiotic, the imbalance of the concentration of doxycycline hydrochloride (DOX) can cause many harms, so real-time detection of the DOX content is crucial. In this study, Galla chinensis residue (GCR) was used as a carbon source, m-phenylenediamine was used as an N-doping agent, and blue-green fluorescent carbon dots (N-GCRCDs) were prepared by a simple hydrothermal synthesis method, with a high quantum yield of 27.31 %. Under optimized conditions, a specific fluorescent probe was established to detect DOX. The addition of DOX resulted in a significant decrease in fluorescence intensity, with a detection range of 5.7–114.9 μM and the detection limit was 1.38 μM. Finally, the feasibility of this method was validated in human urine and the experimental results exhibited a DOX recovery rate of 97.45–104.41 % and an RSD of 0.91–2.64 %. The quenching mechanism was mainly attributed to the inner filter effect and static quenching. Furthermore, the potential application of N-GCRCDs in cells was studied and biocompatibility was evaluated using HepG2 cells, which showed low toxicity at concentrations of 0–50 μg/mL and successful application for HepG2 cell imaging. This study provides reference for resource utilization of GCR and quantitative detection of antibiotics.
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INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2025
·
IF 5.2
Li Xiang,Xianjing Xiang,Qiangqiang Jiao,Yu Luo,Guodong Zeng,Wenhui Zhang,Yuting Qin,Yuping Chen
Rapid proliferation underlies the abnormal expansion of activated hepatic stellate cells (aHSCs) and thereby contributes to the development and progression of liver fibrosis, so inhibition of HSC proliferation serves as a good antifibrotic strategy. As a potent topoisomerase II inhibitor, doxorubicin (DOX), an antineoplastic drug, exhibits a significant antifibrotic activity in vitro via retarding the growth of aHSCs and reversing their myofibroblastic phenotype, but its severe hepatotoxicity, cardiotoxicity, and renal toxicity limit its wide clinical application. Therefore, enhancing the specificity and efficacy of DOX in targeting aHSCs to improve its therapeutic index and minimize its adverse effects has become a key point for the success of DOX in antifibrotic treatment. In this study aimed at liver fibrosis treatment, we combined the excellent drug-loading capability and good biocompatibility of black phosphorus nanosheets (BPNSs), the protective and camouflaging properties of red blood cell membrane encapsulation, and the HSCs-targetability provided by the surface modification with vitamin A derivatives, into the construction of HSCs-targeted BP/DOX nanovesicles (BP/DOX@RMV-VA). The obtained DOX nanovesicles exhibited a uniform particle size and spheroid morphology, excellent diffusion property and stability, and high DOX loading. Specifically, they demonstrated outstanding biosafety, effective HSCs-targetability both in vivo and in vitro, and markedly improved pharmacokinetic profile of DOX. BP/DOX@RMV-VA produced strong antiproliferative and MF-phenotype reverting activity both in cultured aHSCs and in mice chronically injured by CCl 4 . And accordingly, the administration of BP/DOX@RMV-VA to CCl 4 -injured mice effectively suppressed the expansion of aHSCs and fibrogenesis, and significantly improved liver structure and function without causing detectable cardiotoxicity. These results highly suggest the therapeutic potential of BP/DOX@RMV-VA in treating liver fibrosis and other fibrosis-associated liver diseases.
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TALANTA
·
2024
·
IF 5.6
Songjia Luo,Qingliu Wu,Lu Wang,Hao Qu,Lei Zheng
Electrochemical aptamer-based biosensors (EABs) have been developed for multiple important biomarkers for their convenient and real-time features. However, the application of EABs in complex biological fluids has been limited by the rapid loss of sensitivity and selectivity due to inactivation and biofouling of aptamer probes and electrodes. To address this issue, we report the preparation of a simple hydrogel-protected aptamer-based biosensor (HP-EAB) for direct detection of Doxorubicin (DOX) in whole blood. The aptamer provides excellent selectivity for the electrochemical sensor, allowing the prepared sensor to accurately detect DOX in a 50-fold diluted whole blood sample. The agarose hydrogel coating on the electrode surface allows the passage of small molecules while hindering the adsorption of biomolecules from the whole blood matrix to the electrode surface. The experimental results show that the prepared HP-EAB has high stability compared with the unprotected EAB, and the HP-EAB maintains excellent detection performance after 7 days of storage. The hydrogel coating can effectively reduce the non-specific response to the whole blood matrix and prolong the life-time of the sensor. When used to detect DOX in rabbit whole blood, the HP-EAB exhibited excellent detection performance with a detection limit of 25.9 nM (S/N = 3) and a detection range of 0.1 μM–50 μM. The developed HP-EAB provides an excellent platform for the rapid and accurate determination of important analytes in complex biological fluids.
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ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Guanyu Ruan,Lixiang Ye,Jianxi Ke,Hongyu Lin,Minxia Wu,Zhihong Liu,Yu Fang,Shuihua Zhang,Hongmei Wang,Yongsheng Liu,Hongtao Song
Efficiently overcoming chemoresistance in tumor microenvironments remains a critical hurdle in cancer therapy due to tumor heterogeneity, limited drug penetration, and adaptive resistance mechanisms. Herein, we report the design and application of all-in-one gadolinium–doxorubicin nanoassemblies (GDNAs) for spatially targeted delivery and chemoresistance reversal. These multifunctional nanoassemblies integrate a lanthanide-based component for real-time imaging and doxorubicin for chemotherapy, coupled with bioinformatics-guided small interfering RNAs (siRNAs) to silence key resistance-associated genes such as BCL2 and BIRC5. The GDNAs demonstrate enhanced tumor penetration and specificity for chemoresistant cells, achieving deep tissue delivery and synergistic effects in human-derived organoids and xenograft breast cancer models. Remarkably, GDNAs significantly reduce tumor viability and growth while attenuating invasive potential, showcasing superior therapeutic efficacy compared to conventional treatments. Comprehensive preclinical evaluations confirm their biocompatibility and low systemic toxicity, underscoring the translational potential of this platform. This work introduces a paradigm-shifting strategy by integrating imaging, targeted therapy, and gene silencing to address chemoresistance, offering a versatile approach for personalized cancer treatment.
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JOURNAL OF CONTROLLED RELEASE
·
2017
·
IF 7.786
Songzhi Xie,Long Zhao,Xiaojie Song,Maosheng Tang,Chuanfei Mo,Xiaohong Li
The use of bacteria as drug carriers meets several challenges, such as biocompatibility, motility deterioration after drug loading and lack of in vivo verification. Escherichia coli Nissle 1917 (EcN) is one of the best studied probiotic strains, and doxorubicin (DOX) is conjugated onto EcN in the current study via acid-labile linkers of cis -aconitic anhydride (EcN-ca-Dox), realizing the bacteria-directed accumulation and acid-responsive release of anticancer drugs in tumors. The drug conjugation has maintained the bacterial motion profiles of over 9 μm/s and cell viability of over 70%. After 3 h and 3 days of intravenous injection of EcN-ca-Dox, DOX accumulations in tumors are determined as 12.9% and 6.4% of the injected doses per gram of tissue, respectively, which are much higher than the commonly used nanocarriers . Compared with free DOX and DOX-conjugated EcN via stable linkers of succinic anhydride , the EcN-ca-Dox treatment improves the antitumor efficacy with respect to the tumor growth inhibition, prolongation of animal survivals, and apoptosis induction of tumor cells. In addition, EcN has been cleaned off from tumors and other tissues after antimicrobial treatment. Thus, the acid-labile EcN conjugates provide a safe and concise strategy to enhance the temporal and spatial controllability of anticancer drugs.
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BIOMEDICINE & PHARMACOTHERAPY
·
2020
·
IF 4.545
Yuling Bao,Qian Hu,Xiuping Wang,Xiaobo Feng,Yu He,Yuanyuan Guo,Dehao Fu
There are plenty of evidences to show that combining of chemotherapy and immunotherapy should be a very potent anti-cancer therapeutic method. In this research, we evaluated the anti-tumor activity of doxorubicin prodrug combined with erythrocyte membrane-enveloped polymer nano-vaccine against tumor in vitro and in vivo . We also analyzed the immune cell populations to investigate the effect in the tumor microenvironment and explored the inhibitory of lung metastasis. Our study showed that chemo-immunotherapy could inhibit the growth of melanoma tumor in mice. This combination approach promoted a stronger immune response by up-regulating the expression of dendritic cells and cytotoxic T cells in lymph nodes and increased the secretion of cytokines. It also restricted the immunosuppressive environment through inhibiting expression of regulatory T cells. It suggested that combination of prodrug and nano-vaccine achieved better anti-tumor effect than monotherapy, which should be widely valued and further studied to establish in a more economical and efficient way, expected to apply in the future clinical practice of cancer treatment.
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