Materials Science and Engineering B-Advanced Functional Solid-State Materials
·
2017
·
IF 2.552
Zhifeng Xu,Peihong Deng,Junhua Li,Li Xu,Siping Tang
In this work, a new type of fluorescent probe for detection of doxorubicin has been constructed by the combined use of fluorescence resonance energy transfer (FRET) technology and molecular imprinting technique (MIT). Using doxorubicin as the template, the molecularly imprinted polymer thin layer was fabricated on the surfaces of carbon dot (CD) modified silica by sol-gel polymerization. The excitation energy of the fluorescent donor (CDs) could be transferred to the fluorescent acceptor (doxorubicin). The FRET based fluorescent probe demonstrated high sensitivity and selectivity for doxorubicin. The detection limit was 13.8 nM. The fluorescent probe was successfully applied for detecting doxorubicin in doxorubicin-spiked plasmas with a recovery of 96.8–103.8%, a relative standard deviation (RSD) of 1.3–2.8%. The strategy for construction of FRET-based molecularly imprinted materials developed in this work is very promising for analytical applications.
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高影响因子
JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY
·
2017
·Vol. 17
·期 5
·2873-2880
·
IF 1.483
Huang Saiyan,Liu Jieying,Zhu Hao,Hussain Abid,Liu Qing,Li Jing,Shen Yuanyuan,Cheng Jiejun,Guo Shengrong
A novel folate-polyethylene glycol-succinic acid-doxorubicin conjugate (FA-PEG-SA-DOX) micelle loaded with curcumin (CUR) is designed and prepared to target tumor cells via folate-folate receptor interactions and co-deliver chemotherapeutic agent DOX and chemosensitizer CUR for treatment
of multidrug resistant human breast cancer MCF-7/ADR cells. The CUR/FA-PEG-SA-DOX micelles are characterized with the average size of 90.64±0.15 nm and the zeta potential of −15.3±0.8 mV. The CUR and DOX contents of the micelles are 12.07 and 15.69% (w/w), respectively.
The cytotoxicity, cellular uptake and effiux of the micelles are investigated by using MCF-7/ADR cells. The results demonstrate that the CUR/FA-PEG-SA-DOX micelles have greater toxicity (IC50 = 3.10 µg/ml) compared to the free DOX (IC50 = 31.99 µg/ml),
moreover, the micelles present increased cellular uptake and reduced cellular effiux. The combination index of CUR/FA-PEG-SA-DOX micelles was 0.17, which indicate a strong synergistic antitumor efficacy against MCF-7/ADR cells. These results suggest that Curcumin-loaded FA-PEG-SA-DOX micelles
may be a promising nanomedicine for co-delivery dual-drug treatment for cancer.
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高影响因子
Bioactive Materials
·
2017
·
IF 0
Tianmu Hu,Anwar Saeed Ahmed Qahtan,Lei Lei,Zhixin Lei,Dapeng Zhao,Hemin Nie
In order to improve the release pattern of chemotherapy drug and reduce the possibility of drug resistance, poly(ethylene glycol amine) (PEG)-modified alginate microparticles (ALG-PEG MPs) were developed then two different mechanisms were employed to load doxorubicin (Dox): 1) forming Dox/ALG-PEG complex by electrostatic attractions between unsaturated functional groups in Dox and ALG-PEG; 2) forming Dox-ALG-PEG complex through EDC-reaction between the amino and carboxyl groups in Dox and ALG, respectively. Additionally, tuftsin (TFT), a natural immunomodulation peptide, was conjugated to MPs in order to enhance the efficiency of cellular uptake. It was found that the Dox-ALG-PEG-TFT MPs exhibited a significantly slower release of Dox than Dox/ALG-PEG-TFT MPs in neutral medium, suggesting the role of covalent bonding in prolonging Dox retention. Besides, the release of Dox from these MPs was pH-sensitive, and the release rate was observably increased at pH 6.5 compared to the case at pH 7.4. Compared with Dox/ALG-PEG MPs and Dox-ALG-PEG MPs, their counterparts further conjugated with TFT more efficiently inhibited the growth of HeLa cells over a period of 48 h, implying the effectiveness of TFT in enhancing cellular uptake of MPs. Over a period of 48 h, Dox-ALG-PEG-TFT MPs inhibited the growth of HeLa cells less efficiently than Dox/ALG-PEG-TFT MPs but the difference was not significant ( p > 0.05). In consideration of the prolonged and sustained release of Dox, Dox-ALG-PEG-TFT MPs possess the advantages for long-term treatment.
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PubMed
ACS Applied Materials & Interfaces
·
2017
·
IF 7.504
Haiqiu Wu,Haojie Jin,Cun Wang,Zihao Zhang,Haoyu Ruan,Luyan Sun,Chen Yang,Yongjing Li,Wenxin Qin,Changchun Wang
Combination chemotherapy has been proposed to achieve synergistic effect and minimize drug dose for cancer treatment in clinic application. In this article, the stimuli-responsive polymeric nanogels (<100 nm in size) based on poly(acrylic acid) were designed as codelivery system for doxorubicin and cisplatin to overcome drug resistance. By chelation, electrostatic interaction, and π–π stacking interactions, the nanogels could encapsulate doxorubicin and cisplatin with designed ratio and high capacity. Compared with free drugs, the nanogels could deliver more drugs into MCF-7/ADR cells. Significant accumulation in tumor tissues was observed in the biodistribution experiments. The in vitro antitumor studies demonstrated the superior cell-killing activity of the nanogel drug delivery system with a combination index of 0.84, which indicated the great synergistic effect. All the antitumor experimental data revealed that the combination therapy was effective for the multidrug-resistant MCF-7/ADR tumor with reduced side effects.
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高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Yuqi Wu,Jiawei Li,Liang Liu,Xinhong Chu,Min Zhong,Hongkun Li,Chengcheng Zhao,Hui Fu,Yujiao Sun,Yingpeng Li
The oral delivery of doxorubicin (DOX), an anti-cancer drug, encounters multiple hurdles such as limited gastrointestinal permeability, P-glycoprotein-mediated efflux, brief intestinal residence, and rapid degradation. This study introduced a novel approach utilizing hyaluronic acid (HA)-grafted fatty acid monoglycerides (HGD) to encapsulate DOX, forming HGD-DOX nanoparticles, aimed at enhancing its oral bioavailability. Drug encapsulated by HGD provided several advantages, including extended drug retention in the gastrointestinal tract, controlled release kinetics, and promotion of lymphatic absorption in the intestine. Additionally, HGD-DOX nanoparticles could specifically target CD44 receptors, potentially increasing therapeutic efficacy. The uptake mechanism of HGD-DOX nanoparticles primarily involved clathrin-mediated, caveolin-mediated and macropinocytosis endocytosis. Pharmacokinetic analysis further revealed that HGD significantly prolonged the in vivo residence time of DOX. In vivo imaging and pharmacodynamic studies indicated that HGD possessed tumor-targeting capabilities and exhibited a significant inhibitory effect on tumor growth, while maintaining an acceptable safety profile. Collectively, these findings position HGD-DOX nanoparticles as a promising strategy to boost the oral bioavailability of DOX, offering a potential avenue for improved cancer treatment.
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高影响因子
MOLECULAR PHARMACEUTICS
·
2024
·
IF 4.5
Wei Lin,Anyin Li,Lin Qiu,Hai Huang,Pengfei Cui,Jianhao Wang
One of the most significant reasons hindering the clinical translation of nanomedicines is the rapid clearance of intravenously injected nanoparticles by the mononuclear phagocyte system, particularly by Kupffer cells in the liver, leading to an inefficient delivery of nanomedicines for tumor treatment. The threshold theory suggests that the liver’s capacity to clear nanoparticles is limited, and a single high dose of nanoparticles can reduce the hepatic clearance efficiency, allowing more nanomedicines to reach tumor tissues and enhance therapeutic efficacy. Building upon this theory, researchers have conducted numerous validation studies based on the same nanoparticle carrier systems. These studies involve the use of albumin nanoparticles to improve the therapeutic efficacy of albumin nanomedicines as well as polyethylene glycol (PEG)-modified liposomal nanoparticles to enhance the efficacy of PEGylated liposomal nanomedicines. However, there is no research indicating the feasibility of the threshold theory when blank nanoparticles and nanomedicine belong to different nanoparticle carrier systems currently. In this study, we prepared two different sizes of albumin nanoparticles by using bovine serum albumin. We used the marketed nanomedicine liposomal doxorubicin hydrochloride injection (trade name: LIBOD, manufacturer: Shanghai Fudan-zhangjiang Biopharmaceutical Co., Ltd.), as the representative nanomedicine. Through in vivo experiments, we found that using threshold doses of albumin nanoparticles still can reduce the clearance rate of LIBOD, prolong its time in vivo, increase the area under the plasma concentration–time curve (AUC), and also lead to an increased accumulation of the drug at the tumor site. Furthermore, evaluation of in vivo efficacy and safety further indicates that threshold doses of 100 nm albumin nanoparticles can enhance the antitumor effect of LIBOD without causing harm to the animals. During the study, we found that the particle size of albumin nanoparticles influenced the in vivo distribution of the nanomedicine at the same threshold dose. Compared with 200 nm albumin nanoparticles, 100 nm albumin nanoparticles more effectively reduce the clearance efficiency of LIBOD and enhance nanomedicine accumulation at the tumor site, warranting further investigation. This study utilized albumin nanoparticles to reduce hepatic clearance efficiency and enhance the delivery efficiency of nonalbumin nanocarrier liposomal nanomedicine, providing a new avenue to improve the efficacy and clinical translation of nanomedicines with different carrier systems.
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高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2024
·
IF 6.9
Jaili Li,Ting Luo,Yao Zhao,Dou Wang,Yuanxiang Jin,Zufang Wu,Guiling Yang,Xingjiang Qi
Doxorubicin (DOX) is a commonly used anthracycline in cancer chemotherapy. The clinical application of DOX is constrained by its cardiotoxicity. Myricetin (MYR) is a natural flavonoid widely present in many plants with antioxidant and anti-inflammatory properties. However, MYR's beneficial effects and mechanisms in alleviating DOX-induced cardiotoxicity (DIC) remain unknown. C57BL/6 mice were injected with 15 mg/kg of DOX to establish the DIC, and MYR solutions were administrated by gavage to investigate its cardioprotective potentials. Histopathological analysis, physiological indicators assessment, transcriptomics analysis, and RT-qPCR were used to elucidate the potential mechanism of MYR in DIC treatment. MYR reduced cardiac injury produced by DOX, decreased levels of cTnI, AST, LDH, and BNP, and improved myocardial injury and fibrosis. MYR effectively prevented DOX-induced oxidative stress, such as lowered MDA levels and elevated SOD, CAT, and GSH activities. MYR effectively suppressed NLRP3 and ASC gene expression levels to inhibit pyroptosis while regulating Caspase1 and Bax levels to reduce cardiac cell apoptosis. According to the transcriptomic analysis, glucose and fatty acid metabolism were associated with differential gene expression. KEGG pathway analysis revealed differential gene enrichment in PPAR and AMPK pathways, among others. Following validation, MYR was found to alleviate DIC by regulating glycolipid metabolism and AMPK pathway-related genes. Our findings demonstrated that MYR could mitigate DIC by regulating the processes of oxidative stress, apoptosis, and pyroptosis. MYR is critical in improving DOX-induced myocardial energy metabolism abnormalities mediated by the AMPK signaling pathway. In conclusion, MYR holds promise as a therapeutic strategy for DIC.
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高影响因子
JOURNAL OF SEPARATION SCIENCE
·
2025
·Vol. 48
·期 8
·e70249
·
IF 2.8
Tian Yawen,Jiang Xinhui,Wang Jie,Cui Jiaping,Fu Xinru,Xia Zhining,Huang Yike
In this study, dual stimulus-response molecularly imprinted hydrogels (MIHs) with water-soluble doxorubicin (DOX) as the imprinted molecule were developed for improving the selective specific recognition capacity. By using N-isopropylacrylamide (NIPAM) as a temperature-sensitive monomer, and N-[3-(dimethylamino)propyl]methacrylamide (DMAPMA) as a pH-responsive functional monomer, a series of MIHs with different concentration ratios of dual functional monomers and cross-linker were prepared to study the influencing factors of selective recognition. The results show the prepared MIHs have different rigidity and flexibility under different synthesis conditions. The MIH7 with good adsorption performance and specific recognition ability was selected with its molar ratio of NIPAM/DMAPMA/cross-linker (200/10/100). Its imprinting factor of DOX was as high as 2.26. Adsorption kinetic and adsorption thermodynamic studies showed that MIH7 and DOX had high affinity, and its affinity constant K D was as high as 9.11 × 10 −6 mol/L. For selectivity adsorption, the MIH7 had excellent selectivity at pH 5, with a selectivity factor as high as 1.97 for epirubicin, which is extremely similar in structure, and selectivity factors as high as 6 and 7.68 for idarubicin and oxytetracycline, respectively. The prepared MIH7 was well separated with good specific recognition of DOX in the serum samples, which provided a potential strategy based on the dual stimulus-response and cross-linker for the efficient recognition of water-soluble molecules.
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高影响因子
ACS Omega
·
2025
·
IF 4.3
Na Feng,Junjie Chang,Honglei Yu,Tongfei Li,Lin Lei,Xiaomin Huang,Dandan Shi,Rui Liu,Wenjun Zhang,Xiju He
Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related death worldwide. Doxorubicin (Dox), a conventional chemotherapeutic agent, exhibits unsatisfactory efficacy in HCC due to its poor tumor response, severe cardiotoxicity, and drug resistance. It is urgent to develop strategies to mitigate the side effects and enhance the chemosensitivity of conventional chemotherapy drugs. Traditional Chinese medicine has gained research interest in cancer treatment due to its homology with food and minimal side effects. Puerarin (Pue) has been identified as an effective inhibitor of tumor cell proliferation. However, puerarin’s poor water solubility and bioavailability limit its pharmaceutical application. In this study, a novel puerarin nanoparticle (nanoPue) was developed to overcome its limitation. NanoPue could significantly inhibit tumor growth and enhance the chemotherapeutic effect of Dox in HCC models. NanoPue could increase the perivascular coverage within the tumors; decrease the expressions of NSUN2, p-AKT, VEGFA, and MMP-9; and reduce endothelial cell tube formation. In summary, nanoPue improves Dox therapeutic efficacy by decreasing angiogenic factors via regulating NSUN2 in HCC. This study may provide a potential avenue for advancing nanoPue to enhance chemotherapeutic agents in HCC therapy and supply a theoretical support for the clinical application of nanoPue.
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高影响因子
MOLECULAR PHARMACEUTICS
·
2024
·
IF 4.5
Tingjun Dong,Ning Yang,Jian Qin,Chengcheng Zhao,Tingyu Gao,Hao Ma,Caili Zhu,Huan Xu
Renal fibrosis plays a key role in the pathogenesis of chronic kidney disease (CKD), in which the persistent high expression of transforming growth factor β1 (TGF-β1) and α-smooth muscle actin (α-SMA) contributes to the progression of CKD to renal failure. In order to improve the solubility, bioavailability, and targeting of tanshinone IIA (Tan IIA), a novel targeting material, aminoethyl anisamide-polyethylene glycol-1,2-distearoyl-sn-glycero-3-phosphate ethanolamine (AEAA-PEG-DSPE, APD) modified Tan IIA liposomes (APD-Tan IIA-L) was constructed. An animal model of glomerulonephritis induced by doxorubicin in BALB/c mice was established. APD-Tan IIA-L significantly decreased blood urea nitrogen and serum creatinine (SCr), and the consequences of renal tissue oxidative stress indicators showed that APD-Tan IIA-L downregulated malondialdehyde, upregulated superoxide dismutase, catalase, and glutathione peroxidase. Masson’s trichrome staining showed that the deposition of collagen in the APD-Tan IIA-L group decreased significantly. The pro-fibrotic factors (fibronectin, collagen I, TGF-β1, and α-SMA) and epithelial–mesenchymal transition marker (N-cadherin) were significantly inhibited by APD-Tan IIA-L. By improving the microenvironment of fibrotic kidneys, APD-Tan IIA-L attenuated TGF-β1-induced excessive proliferation of fibroblasts and alleviated oxidative stress damage to the kidney, providing a new strategy for the clinical treatment of renal fibrosis.
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高影响因子
Nanomaterials
·
2024
·Vol. 14
·期 10
·864
·
IF 4.4
Xiao-Min Cao,Yuan-Qiu Cheng,Meng-Meng Chen,Shun-Yu Yao,An-Kang Ying,Xiu-Zhen Wang,Dong-Sheng Guo,Yue Li
Chemotherapy is one of the most commonly used methods for treating cancer, but its side effects severely limit its application and impair treatment effectiveness. Removing off-target chemotherapy drugs from the serum promptly through adsorption is the most direct approach to minimize their side effects. In this study, we synthesized a series of adsorption materials to remove the chemotherapy drug doxorubicin by modifying MOF nanosheets with sulfonated azocalix[4]arenes. The strong affinity of sulfonated azocalix[4]arenes for doxorubicin results in high adsorption strength (Langmuir adsorption constant = 2.45–5.73 L mg−1) and more complete removal of the drug. The extensive external surface area of the 2D nanosheets facilitates the exposure of a large number of accessible adsorption sites, which capture DOX molecules without internal diffusion, leading to a high adsorption rate (pseudo-second-order rate constant = 0.0058–0.0065 g mg−1min−1). These adsorbents perform effectively in physiological environments and exhibit low cytotoxicity and good hemocompatibility. These features make them suitable for removing doxorubicin from serum during “drug capture” procedures. The optimal adsorbent can remove 91% of the clinical concentration of doxorubicin within 5 min.
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高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2015
·
IF 3.65
Song Shen,Lin Wu,Jiejie Liu,Meng Xie,Haijun Shen,Xueyong Qi,Yongmin Yan,Yanru Ge,Yi Jin
To facilitate targeting drug delivery and combined therapy, we develop titanium dioxide-encapsulated Fe 3 O 4 nanoparticles (Fe 3 O 4 @TiO 2 NPs). Titanium dioxide (TiO 2 ), which is employed as a sonosensitizer for sonodynamic therapy (SDT), can also be used for the loading of doxorubicin (DOX). The fabricated Fe 3 O 4 @TiO 2 NPs exhibit pH-dependent loading and release of doxorubicin (DOX) in vitro. After incubation with cancer cells, reactive oxygen species (ROS) are generated efficiently upon the irradiation of ultrasound. In the biodistribution experiments, extremely high in vivo tumor accumulation of Fe 3 O 4 @TiO 2 NPs and long-time retention effect are observed. Compared with chemotherapy or sonodynamic treatment alone, the combined therapy demonstrated a synergistic effect, resulting in stronger cytotoxicity and higher therapeutic efficacy. Thus, the constructed NPs are endowed with multifunctions which allow them to selectively deliver combinatorial therapeutic payload to tumor with enhanced therapeutic effectiveness and minimal side effects.
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高影响因子
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