COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2024
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IF 4.9
Xiaoming Chen,Shun Liu,Mo Shen,Zhipeng Song,Sudu Bilige,Jingkang Li,Yueti Li,Chungang Wu,Liangliang Sun,Jishun Shi,Zihao Chen,Yong Zhao
Doxorubicin (DOX) has been extensively used in cancer chemotherapy as an antibiotic drug, but when DOX concentration exceeds the threshold value, irreversible liver toxicity and cardiotoxicity can be triggered. Therefore, it is a significant theme to detect DOX concentration of patient blood and metabolites for the optimization of drug dosage. Linear correlation between fluorescence quenching of silicon nanoparticles (SiNPs) and DOX concentration enables SiNPs to present good prospect to address this tricky issue. Inspired by these aspects, we put forward a novel method to synthesize dragonfruit-based SiNPs (DSiNPs) at room temperature, and leverage them in the fiber-optic sensing of urine DOX. Firstly, we investigate a simple and green synthesis method of DSiNPs emitting blue-green fluorescence through a one-step redox reaction at room temperature with organosilane as silicon source and fresh dragonfruit juice as reducing agent. Secondly, depending on optical characterization, we demonstrate mechanism of DSiNPs in the detection of DOX. Thirdly, a fiber-optic sensor is used to measure the fluorescence intensity of DSiNPs under diverse salt concentrations, pH values, and illumination time to explore the tolerance of DSiNPs. Fourthly, based on optimization of parameters and validation of specificity, we acquire linear response range of this method to DOX from 0 to 50 μM with detection limit of 3 μM. Finally, this method is leveraged in the detection of urine DOX, and obtained the recovery rates of 92.30 % and 107.30 %. This method holds excellent potential in the clinical analysis of anti-tumor drugs for the advantages of environmental friendliness and simple operation.
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高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2025
·
IF 5.6
Wenjing Li,Juan Shao,Chuxin Zhang,Guodong Cao,Yitao Yan,Qiongyi Han,Huimei Yu,Yingying Wei,Wenbo Zhang,Jie Zheng,Zhongyuan Guo
Colorectal cancer has emerged as a leading cause of global cancer-related morbidity and mortality, necessitating innovative therapeutic strategies. We developed a desilication-recrystallization method to synthesize Silicalite-1-X (X = 2, 8, 16, 32), a hierarchical porous silica molecular sieve with cost-effectiveness, facile synthesis, and tunable porosity. Its programmable mesoporous structure is achieved by precisely controlling the desilication-recrystallization kinetics. Tunable mesopores with precise diameters of 4–6 nm and 20–30 nm were fabricated by controlling cavity expansion through temporal modulation (2–32 h) of a time-dependent synthesis process. Detailed analysis of drug loading and release profiles revealed that although pore structure modification did not significantly alter drug loading efficiency (DLE), it induced a slight but consistent improvement in drug release rate as pore size increased. Systematic biocompatibility evaluation was conducted through an in vitro human colonic epithelial tissue model complemented by the KM mice in vivo studies. Histopathological analysis confirmed Silicalite-1-X caused minimal cytotoxicity and oxidative stress in healthy colon tissue, preserved mucus secretion, and showed no systemic toxicity. Furthermore, Doxorubicin (DOX) loaded Silicalite-1-X platform (Silicalite-1-DOX-X) exhibited dose-dependent cytotoxic efficacy against colorectal carcinoma in vitro models, confirming its anti-tumor therapeutic potential. Our findings provide a framework for engineering molecular sieves with tunable porosity and a platform for expanding their multifunctional applications in advanced materials.
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高影响因子
CARBOHYDRATE POLYMERS
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2025
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IF 12.5
Yuqi Lu,Longyu Deng,Chunfeng Yin,Jingqin Yang,Shaoyun Shan,Hongying Su
Stimuli-responsive drug carriers based on dynamic covalent bonds, particularly boronate esters, have attracted significant attention for their ability to enable targeted release in specific microenvironments. In this study, an intelligent dextran-based hydrogel was developed through the Hantzsch multicomponent cross-linking strategy integrated with pH-sensitive boronate ester bonding. This hydrogel (DHPD-FPBA) features a dual-network architecture comprising rigid 1,4-dihydropyridine (DHP) covalent networks and dynamic boronate ester cross-links, achieved by employing 4-formylphenylboronic acid (FPBA) as a functional aldehyde component in the Hantzsch reaction. Comprehensive structural and morphological analyses confirmed successful formation, tunable cross-linking density, pronounced pH-dependent swelling and mechanical behavior with rapid framework disintegration under acidic conditions (pH 5.0). Doxorubicin (DOX) was efficiently loaded via boronate ester conjugation and released in a pH-responsive manner, with over 65 % release within 48 h at pH 5.0 compared to less than 25 % at pH 7.4. The release kinetics, which adhered to the Peppas model, indicated a diffusion–erosion coupled mechanism. Furthermore, the hydrogels demonstrated high biocompatibility in cytotoxicity assays, and confocal microscopy revealed efficient cellular internalization of the released DOX. These results underscore the potential of DHPD-FPBA hydrogel as a promising platform for tumor-microenvironment-targeted drug delivery.
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Biomaterials Science
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2020
·Vol. 8
·期 18
·5029-5046
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IF 6.183
Yuanhang Zhou,Chuhang Zhou,Yang Zou,Yao Jin,Shidi Han,Qi Liu,Xinping Hu,Leqi Wang,Yining Ma,Yan Liu
Combination therapy has been proved to be an effective strategy to inhibit metastasis, however, its efficacy is always compromised by the poor delivery efficiency of drugs. In this study, multi pH-sensitive polymer–drug conjugate mixed micelles were fabricated by the self-assembly of PEOz-PLA-ace-Cur, a conjugate of curcumin (Cur) with poly(2-ethyl-2-oxazoline)-poly(D,L-lactide) (PEOz-PLA) through the linkage of the pH-cleavable acetal bond, and PEOz-PLA-imi-DOX, a conjugate of doxorubicin (DOX) with PEOz-PLA through the linkage of the pH-cleavable benzoic imine bond. The mixed conjugate micelles (PP-Cur/PP-DOX-Mix-PMs) with accurately and conveniently controlled mass ratio of the two drugs were demonstrated to have a small particle size (40–128 nm), high drug loading capacity and pH-dependent drug release behavior. Notably, PP-Cur5/PP-DOX1-Mix-PMs exhibited slower DOX release under physiological conditions compared with PEOz-PLA-imi-DOX micelles, resulting in deeply reduced side effects in vivo. Furthermore, the mixed conjugate micelles showed synergistically enhanced inhibition of MDA-MB-231 cell growth and metastasis evidenced by the results of in vitro anti-invasion, wound healing and anti-migration assessment, and in vivo bioluminescence imaging in nude mice, and significant reduction of the side effects of DOX compared with dual drug physically loaded polymeric micelles. Mechanistic studies demonstrated that the possible inhibitory mechanism of PP-Cur5/PP-DOX1-Mix-PMs on tumor metastasis could be assigned to their inhibition of the invasion, migration, intravasation and extravasation of tumor cells. In conclusion, the multi pH-sensitive polymer–drug conjugate mixed micelles with synergistically enhanced anti-tumor and anti-metastasis activity are potential candidates for safe and effective cancer combination therapy.
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Journal of Materials Chemistry B
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2014
·Vol. 2
·期 30
·4901-4910
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IF 0
Wenjie Li,Jing Shi,Chun Zhang,Min Li,Lu Gan,Huibi Xu,Xiangliang Yang
The overexpression of thioredoxin (Trx) 1 is one of the mechanisms for drug resistance in hepatocellular carcinoma (HCC) treatment. The co-delivery of drugs and a short hairpin RNA (shRNA) against Trx1 to silence its expression might provide a promising approach to improve drug sensitivity to chemotherapeutic agents. In this paper, cationic liposomes containing gemini surfactants, soybean lecithin and DOPE were firstly constructed as gene transfection carriers. The length and symmetrical degree of aliphatic chains of gemini surfactants were found to affect gene transfection efficiency of cationic liposomes. Cationic liposome containing gemini surfactants with symmetrical C16 aliphatic chains (L16-2-16) showed the highest transfection efficiency in HCC Bel7402 cells and also displayed the strongest DNA condensation capacity and the highest cellular uptake. Folic acid (FA) targeting further enhanced the transfection efficiency of L16-2-16 by binding to the folate receptor (FR) in FR-overexpressing Bel7402 cells and lipid raft/caveolae-dependent endocytosis might be involved in FA-L16-2-16-mediated gene delivery. Then the multifunctional co-delivery system for doxorubicin (DOX) and Trx1 shRNA was developed via electrostatic interactions between the FA-L16-2-16 and Trx1 shRNA/DOX complex. Co-delivery of Trx1 shRNA and DOX by FA-L16-2-16 inhibited the cell viability and induced apoptosis of Bel7402 cells more efficiently than co-delivery of control shRNA and DOX. The system for co-delivering DOX and Trx1 shRNA could simultaneously achieve gene transfection and drug release in the same cell and increase the intracellular as well as intranuclear DOX concentrations. These results demonstrated that gemini surfactant-based cationic liposomes were promising carriers for the co-delivery of nucleic acids and chemotherapeutic agents to sensitize HCC chemotherapy.
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Molecular Medicine Reports
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2016
·Vol. 14
·期 3
·2853-2859
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IF 1.559
Feng Ding,Tianfeng Liu,Nina Yu,Shihong Li,Xiaofei Zhang,Guanghong Zheng,Chunming Lv,Kai Mou,Jia Xu,Bo Li,Surong Wang,Haibo Song
Nitidine chloride (NC) exhibits anti-tumor properties in various types of tumor. However, to the best of our knowledge there is no previous evidence of NC involvement in the apoptosis or proliferation of ovarian cancer cells and the underlying molecular mechanisms. The present study aimed to investigate the influence of NC on the viability and apoptosis of ovarian cancer cells and the synergistic effect NC and doxorubicin (DOX) may have on ovarian cancer cells. The viability and proliferation of ovarian cancer cells were examined using a methyl thiazolyl tetrazolium assay and 3H-thymidine incorporation assay. The apoptotic rate of ovarian cancer cells was detected by flow cytometry. The expression of apoptosis‑associated proteins and Akt serine/threonine kinase 1 (Akt) were determined by western blot analysis following NC treatment. The inhibitory effect of NC on the proliferation of ovarian cancer cells was demonstrated in a time and dose‑dependent manner. The pro-apoptotic effect of NC on ovarian cancer cells was also observed. It was determined that NC significantly downregulated the protein expression levels of B‑cell CLL/lymphoma 2 (Bcl-2) and upregulated the expression of Bcl‑2‑associated X protein, p53, caspase‑3 and ‑9. NC suppressed Akt phosphorylation. Additionally, the present study demonstrated that the effect of NC on the proliferation and apoptosis of ovarian cancer cells was Akt‑dependent by using the phosphatidylinositol-4,5-bisphosphate 3-kinase/Akt signaling pathway inhibitor, LY294002. NC exhibited a synergistic inhibitory effect on the viability of ovarian cancer cells when combined with DOX. The current study demonstrated that NC inhibited the proliferation and induced the apoptosis of ovarian cancer cells via the Akt signaling pathway and highlighted its potential clinical application for the treatment of ovarian cancer.
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高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
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2018
·
IF 6.02
Jing Zhao,Jingjing Du,Yang Pan,Tingting Chen,Lihui Zhao,Yanmeng Zhu,Yingfu Chen,Yuyang Zheng,Yu Liu,Lihua Sun,Pengzhou Hang,Zhimin Du
Brain-derived neurotrophic factor (BDNF)/tropomyosin-related receptor kinase B (TrkB) pathway has been revealed as a novel therapeutic target for several neurological diseases . Recently, small-molecule TrkB agonist 7,8-dihydroxyflavone (7,8-DHF) has received considerable attention as a novel potential candidate for the treatment of various BDNF-implicated human disorders. However, its roles in cardiac diseases are not fully understood. Here, the present study aimed to clarify the effects and mechanisms of 7,8-DHF on doxorubicin (Dox)-induced cardiotoxicity . Kunming mice and H9c2 cells were employed to investigate the functional role of 7,8-DHF both in vivo and in vitro. 7,8-DHF markedly increased cell viability and reduced cell death of Dox-treated cells. Meanwhile, 7,8-DHF significantly increased mitochondrial respiration , membrane potential, and optic atrophy 1 (OPA1) protein expression . 7,8-DHF improved cardiac function and attenuated cardiac injury in Dox mice model. Expression of AMP-activated protein kinase (AMPK) and signal transducers and activators of transcription 3 (STAT3) was restored by 7,8-DHF. Furthermore, the protective role of 7,8-DHF was abolished by ANA-12 (a specific antagonist of TrkB). In elucidating the molecular mechanism, the phosphorylation of Akt was significantly increased while extracellular regulated protein kinase (ERK) was decreased after 7,8-DHF treatment. The regulatory effects of 7,8-DHF on STAT3 and AMPK was reversed by Akt inhibitor . In summary, 7,8-DHF attenuated Dox-induced cardiotoxicity by activating Akt and increasing mitochondrial oxidative phosphorylation and thereby regulating STAT3, AMPK, and ERK signals. The present study enhanced current understanding of TrkB receptor in the cardiovascular system and provided a novel target for prevention and treatment of heart diseases.
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JOURNAL OF MOLECULAR LIQUIDS
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2020
·
IF 5.065
Yushu Wu,Min Liu,Wenxin Pei,Yanna Zhao,Danfeng Wang,Tingting Liu,Bin Sun,Qingpeng Wang,Jun Han
DNA nanostructures-based chemotherapy-phototherapy (CTPT) combination therapy can achieve targeted release and effectively overcome multidrug resistance (MDR). The therapeutic effect of CTPT combination drugs loaded in DNA nanostructures is related to the interactions among them. Herein, based on our previous research on AS1411NTrs loading with a single drug of DOX , the interactions between a single drug (toluidine blue O, TBO) or combination drugs (doxorubicin and toluidine blue O, DOX + TBO) and AS1411 aptamer-tethered DNA nanotrains (AS1411NTrs) were investigated. By fluorescence spectroscopy and isothermal titration calorimetry technique, the corresponding thermodynamic parameters were obtained, including the number of binding sites, binding constant , enthalpy change and entropy change. By combining with the differential scanning calorimetry and ferrocyanide ion quenching analysis, the binding mode-thermodynamic parameters were correlated. In addition, the effect of the binding affinity of DOX and TBO to AS1411NTrs on the drugs release rate was studied. Finally, the in vitro cytotoxicity and confocal laser scanning microscopy imaging of AS1411NTrs + TBO + DOX was investigated. The results showed that this drug delivery system could increase its in vitro cytotoxicity and overcome drug resistance in DOX-resistant human breast cancer cells (MCF-7/ADR). The work would provide important information for the combination therapy of DOX and TBO to overcome MDR effectively.
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JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2024
·
IF 4.5
Yu Wang,Lisi Yan,Xu Yan,Jianqiang Ding,Bo Cheng,Jing Yang,Binbin Li,Xinyu Wang
The micro-nano structure of drug delivery systems, which realize the release of the drug in stages, represent a promising therapeutic approach for tumor chemotherapy. In this study, we developed a drug delivery system in which nano-PLGA was coated on the surface of attapulgite microspheres (ATT-MS) loaded with doxorubicin hydrochloride (DOX). Nano-PLGA surrounding ATT-MS formed a satellite structure, which improved the drug release rate by blocking the drug release channels with the nano-PLGA. The drug delivery system achieves a high DOX encapsulation efficiency (98 %) and enables passive, tumor-selective drug release. The zeta potential and drug release curve showed that DOX in this drug delivery system is more readily released in the tumor microenvironment. The fluorescence imaging and Western blot analysis showed that the drug delivery system has the potential to improve tumor resistance. Moreover, the in vivo experiment showed that the system not only maintained the anticancer activity but also reduced the organ damage. In conclusion, this micro-nano structure of the drug delivery system may provide a novel approach to effectively deliver DOX to the tumor and reduce systemic toxicity.
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高影响因子
ARCHIVES OF TOXICOLOGY
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2024
·
IF 4.8
Wang Yanwei,Qiu Jingru,Yan Hua,Zhang Nan,Gao Shixuan,Xu Ning,Wang Cuiyan,Lou Haiyan
Doxorubicin (DOX) is one of the most frequently used chemotherapeutic drugs belonging to the class of anthracyclines. However, the cardiotoxic effects of anthracyclines limit their clinical use. Recent studies have suggested that ferroptosis is the main underlying pathogenetic mechanism of DOX-induced cardiomyopathy (DIC). BTB-and-CNC homology 1 (Bach1) acts as a key role in the regulation of ferroptosis. However, the mechanistic role of Bach1 in DIC remains unclear. Therefore, this study aimed to investigate the underlying mechanistic role of Bach1 in DOX-induced cardiotoxicity using the DIC mice in vivo (DOX at cumulative dose of 20 mg/kg) and the DOX-treated H9c2 cardiomyocytes in vitro (1 μM). Our results show a marked upregulation in the expression of Bach1 in the cardiac tissues of the DOX-treated mice and the DOX-treated cardiomyocytes. However, Bach1 −/− mice exhibited reduced lipid peroxidation and less severe cardiomyopathy after DOX treatment. Bach1 knockdown protected against DOX-induced ferroptosis in both in vivo and in vitro models. Ferrostatin-1 (Fer-1), a potent inhibitor of ferroptosis, significantly alleviated DOX-induced cardiac damage. However, the cardioprotective effects of Bach1 knockdown were reversed by pre-treatment with Zinc Protoporphyrin (ZnPP), a selective inhibitor of heme oxygenase-1(HO-1). Taken together, these findings demonstrated that Bach1 promoted oxidative stress and ferroptosis through suppressing the expression of HO-1. Therefore, Bach1 may present as a promising new therapeutic target for the prevention and early intervention of DOX-induced cardiotoxicity.
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INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2014
·
IF 3.785
Qian Li,Shixian Lv,Zhaohui Tang,Muhua Liu,Dawei Zhang,Yan Yang,Xuesi Chen
Herein, we develop a co-delivery system of paclitaxel (PTX) and doxorubicin hydrochloride (DOX·HCl) based on methoxypoly(ethylene glycol)- block -poly( l -glutamic acid) (mPEG- b -PLG) for cancer treatment. PTX was grafted to the mPEG- b -PLG by esterification to give mPEG- b -PLG- g -PTX. DOX·HCl was encapsulated via electrostatic interaction and hydrophobic stack between the DOX·HCl and mPEG- b -PLG- g -PTX in aqueous solution. The release rate of DOX·HCl from the drug-loaded nanoparticles (mPEG- b -PLG- g -PTX-DOX) was slow at blood pH (pH 7.4), but obviously increased at endosome pH (pH 5.4). The mPEG- b -PLG- g -PTX-DOX exhibited slight synergistic effect in inhibition of proliferation of A549 and MCF-7 human cancer cells. For in vivo treatment of xenograft human breast tumor (MCF-7), the mPEG- b -PLG- g -PTX-DOX nanoparticles exhibited remarkable tumor inhibition effect with a 95.5% tumor-suppression-rate which was significantly higher than those of related single anticancer agents such as free DOX·HCl and mPEG- b -PLG- g -PTX. These results indicated that the mPEG- b -PLG- g -PTX-DOX would have great potential in cancer therapy.
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高影响因子
ACS Applied Materials & Interfaces
·
2018
·
IF 8.097
Qian Li,Lihong Sun,Mengmeng Hou,Qiubing Chen,Ruihao Yang,Lei Zhang,Zhigang Xu,Yuejun Kang,Peng Xue
Environmental stimuli, including pH, light, and temperature, have been utilized for activating controlled drug delivery to achieve efficient antitumor therapeutics while minimizing undesirable side effects. In this study, a multifunctional nanoplatform based on hollow mesoporous copper sulfide nanoparticles (H-CuS NPs) was developed by loading the interior cavity of the NPs with a drug-loaded phase-change material (PCM, 1-tetradecanol). Doxorubicin (DOX) and chlorin e6 (Ce6) were selected as the model chemotherapeutic drug and photosensitizer, respectively, which were encapsulated in H-CuS NPs via the PCM to form H-CuS@PCM/DOX/Ce6 (HPDC) NPs. When exposed to near infrared laser irradiation, this nanocomplex could produce a strong photothermic effect and thus induce the controlled release of DOX and Ce6 from the melting PCM. Subsequently, the DOX-mediated chemotherapeutic effect and Ce6-mediated photodynamic effect further contributed to enhanced tumor eradication. The efficacy of this multimodal cancer treatment combining chemo-, photothermal, and photodynamic therapies was systematically evaluated both in vitro and in vivo using a 4T1 mouse mammary tumor cell line and a mouse model bearing breast cancer. Moreover, this nanoplatform exhibited minimal systemic toxicity and good hemocompatibility and may provide an effective strategy for the delivery of multiple therapeutic agents and application of multimodal cancer treatments.
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