Journal of Materials Chemistry B
·
2022
·Vol. 10
·期 43
·8996-9007
·
IF 7.571
Xin Zhang,Ning Wang,Yetong Shen,Yang Zhang,Lu Han,Bo Hu
A novel drug loading system, Au@Si–NN–Si@SiO2, is constructed by a layer-by-layer assembly approach. The core Au nanorods serve as the matrix for a near-infrared light (NIR) responsive photothermal feature. Meanwhile, the assembly's middle shell is composed of azobenzene linked silica, which produces free radicals by breaking –NN– bonds at a high temperature brought about by a NIR irradiation-caused photothermal effect, which further triggers the loaded drug release. The outer shell is formed of SiO2 in order to prevent leakage of drug in the middle layer. The fully drug loaded nanocarriers, Au@Si–NN–Si@SiO2-Dox, exhibit an excellent photothermal effect (43%) at a concentration of 170 μg mL−1 under 808 nm NIR laser at 2.3 W cm−2. The antitumor performance of Au@Si–NN–Si@SiO2-Dox was investigated using human colon cancer cells (HCT116) as a model. By combining NIR-triggered drug release, free radical generation and the photothermal effect, the proposed Au@Si–NN–Si@SiO2-Dox exhibits improved antitumor efficiency. By using a dosage of 170 μg mL−1, a cell viability of 17.56% is achieved for HCT116 (5 × 103–1 × 104 cells per well) with 10 min of NIR laser irradiation (808 nm, 2.3 W cm−2). All the results demonstrate that Au@Si–NN–Si@SiO2-Dox exhibits wonderful dosage-dependent antitumor performance and has great potential as a therapeutic agent for tumors or even for use in the clinic.
研究领域:
癌症治疗
·
纳米技术
·
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
RSC Advances
·
2023
·Vol. 13
·期 16
·10840-10846
·
IF 3.9
Qiu-Yan Zhang,Qing-Long Yu,Wei-Jing Luan,Tong-Fang Li,Ya-Ni Xiao,Li Zhang,Yi Li,Rong Rong,Chun-Guang Ren
Colorectal cancer (CRC) is one of the most prevalent cancers worldwide as well as a significant cause of mortality. The conventional treatment could cause serious side effects and induce drug resistance, recurrence and metastasis of cancers. Hence, specific targeting of cancer cells without affecting the normal tissues is currently an urgent necessity in cancer therapy. The emerging of peptide–drug conjugates (PDC) is regarded as a promising approach to address malignant tumors. LWJ-M30, a conjugate of DM1 and B6 peptide, targeted transferrin receptors (TfRs) on the surface of the CRC cells, showing a powerful anti-cancer effect. LWJ-M30 significantly inhibited the HCT116 cells proliferation and migration in vitro. LWJ-M30 also dramatically decreased the level of polymeric tubulin, while the disruption of microtubules caused the cell cycle to be arrested in the G2/M phase. LWJ-M30 induced the HCT116 cells apoptosis both in vivo and in vitro. The results in vivo demonstrated that LWJ-M30 could inhibit the HCT116 growth without affecting the mouse body weight. Taking these results together, our data indicated that LWJ-M30 could improve the therapeutic effects of DM1 while reducing the systemic toxicity in normal tissues.
研究领域:
肿瘤学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2020
·
IF 6.785
Ling Qiu,Xi Li,Gaochao Lv,Yann Seimbille,Ke Li,Ying Peng,Qingzhu Liu,Minhao Xie,Jianguo Lin
Overexpression of legumain is closely associated with tumor proliferation, invasion, and metastasis. Because of its intrinsic properties, such as high sensitivity and resolution, positron emission tomography (PET) has become an effective imaging technique for early diagnosis, treatment response prediction, and monitoring. Herein, two legumain-targeting radiofluorinated smart probes (18F-2 and 18F-3) as well as a control probe (18F-1) were specifically designed for PET imaging of legumain activity in tumors. 18F-1, 18F-2, and 18F-3 were obtained with high radiochemical yield (RCY > 60%) and radiochemical purity (RCP > 99%) using a convenient “one-step” 18F-labeling method. The probes 18F-2 and 18F-3 exhibited high response to legumain activity and reductive environment and revealed comparable uptake in HCT116 cells (4.22% ± 0.14% and 4.64% ± 0.32% for 18F-2 and 18F-3, respectively; 8.46% ± 0.33% and 9.05% ± 0.24% for co-treatment of 18F-2 + 2 and 18F-3 + 3 at 1 h), while the control probe 18F-1 showed no response. PET imaging of tumor-bearing mice showed that the co-injection strategy (18F-2 + 2 and 18F-3 + 3) resulted in higher tumor uptake (3.57% ± 0.37% and 3.72% ± 0.19% ID/g at 10 min, respectively) than the single injection strategy (2.59% ± 0.19% and 2.60% ± 0.46% ID/g for 18F-2 and 18F-3, respectively). In addition, introduction of the trimeric histidine-glutamate (HEHEHE) tag to 18F-3 reduced the liver uptake by almost two-fold without any noticeable effect on the tumor uptake. All the results indicate that 18F-3 holds great potential applications in clinics for sensitive and specific PET imaging of legumain activity in tumors.
研究领域:
医学成像
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癌症研究
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分子生物学
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放射学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2024
·Vol. 25
·期 12
·6468
·
IF 4.9
Yuying Li,Wei Yan,Yu Qin,Liwei Zhang,Sheng Xiao
Chemotherapy resistance in cancer is an essential factor leading to high mortality rates. Tumor multidrug resistance arises as a result of the autophagy process. Our previous study found that compound 1-nitro-2 acyl anthraquinone-leucine (C2) exhibited excellent anti-colorectal cancer (CRC) activity involving autophagy and apoptosis-related proteins, whereas its underlying mechanism remains unclear. A notable aspect of this study is how C2 overcomes the multidrug susceptibility of HCT116/L-OHP, a colon cancer cell line that is resistant to both in vitro and in vivo oxaliplatin (trans-/-diaminocyclohexane oxalatoplatinum; L-OHP). In a xenograft tumor mouse model, we discovered that the mixture of C2 and L-OHP reversed the resistance of HCT116/L-OHP cells to L-OHP and inhibited tumor growth; furthermore, C2 down-regulated the gene expression levels ofP-gpandBCRPand decreasedP-gp’sdrug efflux activity. It is important to note that while C2 re-sensitized the HCT116/L-OHP cells to L-OHP for apoptosis, it also triggered a protective autophagic pathway. The expression levels of cleaved caspase-3 and Beclin 1 steadily rose. Expression of PI3K, phosphorylated AKT, and mTOR were decreased, while p53 increased. We demonstrated that the anthraquinone derivative C2 acts as an L-OHP sensitizer and reverses resistance to L-OHP in HCT116/L-OHP cells. It suggests that C2 can induce autophagy in HCT116/L-OHP cells by mediating p53 and the PI3K/AKT/mTOR signaling pathway.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2019
·Vol. 411
·期 12
·2545-2553
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IF 3.286
Du Fangkai,Li Mengru,Wei Yanye,Huang Donglian,Zhou Yan,Yang Lifang,Chen Jian,Liu Shaogang,Tan Xuecai
The design of vigorous tools for creatinine determination is extremely important in the diagnosis and treatment of kidney diseases. In the study, we examine a robust fluorescent turn-on probe (NCP-Pd) for creatinine detection in a completely aqueous solution based on the metal palladium-catalyzed reaction. In the presence of creatinine, the NCP-Pd dissociates and subsequently restores the fluorescence due to elimination of the heavy atom quenching effect and prevention of the photoinduced electron transfer effect. The probe NCP-Pd displays excellent detecting performance with respect to creatinine such as good water solubility, high selectivity, and a low detection limit (0.16 μM). Additionally, in order to ensure its clinical application, this probe is operated in blood serum samples for detecting creatinine and compared with a commercial clinical method. The results indicate an extremely high agreement with the commercial clinical method. Furthermore, the results confirm that the probe NCP-Pd exhibits satisfactory cell permeability and low cytotoxicity and can detect creatinine in L929 and HCT116 cells. The study provides a potential application for detecting creatinine and conducting pathological research on creatinine-involved diseases.
研究领域:
分析化学
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生物化学
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生物医学工程
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细胞生物学
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临床化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2018
·
IF 6.014
Xichuan Tang,Liwei Tan,Kun Shi,Jinrong Peng,Yao Xiao,Wenting Li,Lijuan Chen,Qian Yang,Zhiyong Qian
Enhancing the heat-sensitivity of tumor cells provides an alternative solution to maintaining the therapeutic outcome of photothermal therapy (PTT). In this study, we constructed a therapeutic system, which was composed of methoxy-polyethylene-glycol-coated-gold-nanorods (MPEG-AuNR) and VER-155008-micelles, to evaluate the effect of VER-155008 on the sensitivity of tumor cells to heat, and further investigate the therapeutic outcome of MPEG-AuNR mediated PTT combined with VER-155008- micelles. VER-155008- micelles down-regulate the expression of heat shock proteins and attenuate the heat-resistance of tumor cell. The survival of HCT116 cells treated with VER-155008- micelles under 45 °C is equal to that treated with high temperature hyperthermia (55 °C) in vitro . Furthermore, we proved either the MPEG-AuNR or VER-155008- micelles can be accumulate in the tumor site by photoacoustic imaging and fluorescent imaging. In vivo anti-cancer evaluation showed that tumor size remarkably decreased (smaller than 100 mm 3 or vanished) when treated with combing 45 °C mild PTT system, which contrasted to the tumor size when treated with individual 45 °C mild PTT (around 500 nm 3 ) or normal saline as control (larger than 2000 nm 3 ). These results proved that the VER-155008- micelles can attenuate the heat-resistance of tumor cells and enhance the therapeutic outcome of mild-temperature photothermal therapy.
研究领域:
纳米技术
·
癌症治疗
·
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
CANCER CHEMOTHERAPY AND PHARMACOLOGY
·
2019
·Vol. 84
·期 3
·527-537
·
IF 3.008
Weng Qi,Zhou Leilei,Xia Lihua,Zheng Yixin,Zhang Xiangli,Li Fengzhi,Li Qingyong
Purpose Recent researches are attempting to verify that the 3D cell models can provide a gap bridge between in vitro and in vivo for anticancer drug evaluations. The aim of this study was to continue the development of novel in vitro 3D cell models and the investigation of the cellular uptake mechanism of camptothecin (CPT) and its derivatives [FL118 (10,11-methylenedioxy-20( S )-camptothecin), 9-Q20 (9- p -trifluoromethylphenyl-10,11-methylenedioxy-20( S )-camptothecin)] in 2D and 3D cell models. Methods The 3D cell models were established using ultralow attachment 96-well plates. The cytotoxicity of CPT, FL118, and 9-Q20 was evaluated by MTT method. The effects of compound concentration, incubation time, temperature, and transporter inhibitors on the cellular uptake of CPT, FL118, and 9-Q20 were examined in 2D and 3D cell models. Results The cytotoxicity of CPT, FL118, and 9-Q20 was lower in 3D cell models than 2D cell models. In 2D Caco-2 cell model, the uptake rate of CPT, FL118, and 9-Q20 was faster during the early time of incubation. In 3D Caco-2 cell model, the uptake capacity of CPT, FL118, and 9-Q20 was significantly improved over time. In 3D Caco-2 cell model, Verapamil (P-gp inhibitor) and Gefitinib (BCRP inhibitor) more significantly increased the uptake of CPT and 9-Q20. In contrast, P-gp and BCRP did not affect the accumulation of FL118 in 2D and 3D Caco-2 cell models. The accumulation of CPT, FL118, and 9-Q20 was greater in HepG2 cells than HCT116 cells. Conclusion The 3D cell models provided more potency information on the process of cellular uptake of CPT, FL118, and 9-Q20, which more objectively reflected the drug sensitivity and drug resistance in vivo compared with the 2D cell models.
研究领域:
药理学
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肿瘤学
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细胞生物学
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药物开发
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2020
·Vol. 44
·期 22
·9304-9312
·
IF 3.288
Simin Wei,Yinghui Wang,Zhishu Tang,Jinhang Hu,Rui Su,Jingjie Lin,Tuan Zhou,Hui Guo,Nan Wang,Rongrong Xu
Green synthesis of silver nanoparticles (AgNPs) has been extensively studied by using a variety of plant extracts for applications in biomedical sciences and engineering. However, there are no reports on the synthesis of AgNPs by utilizing the berry extract of Sea Buckthorn, which is a traditional Chinese medicine and exhibits a wide spectrum of antioxidant, anti-inflammatory and anticancer activities. In this paper, we report an easy and eco-friendly technique for the preparation of AgNPs using the Sea Buckthorn berry extract under ultrasonic radiation at ambient temperature and the evaluation of both biosynthesis parameters and biological activities. The UV-visible spectrum and dynamic light scattering (DLS) analysis showed that the size of AgNPs was sensitive to the biosynthesis parameters, such as the pH of the extract, material proportion and reaction time, offering a size-controlled synthetic method for AgNPs. The X-ray diffraction (XRD), transmission electron microscopy (TEM), selected area electron diffraction (SAED) and DLS studies showed that the AgNPs (pH 10.0; material proportion 1 : 1; 4 h) had a face-centered cubic (fcc) structure and spherical shape with an average particle size of 27.3 ± 0.2 nm covered by anions, and existed in a monodispersed form with a polydispersity index (PDI) of 0.213. The biosynthesized AgNPs showed potent anticancer activity against human colorectal cancer (HCT116 and SW620), hepatoma cancer (HepG2), breast cancer (MCF-7) and cervical cancer (HeLa) cell lines as well as strong antioxidant activity. The IC50 values for these five cell lines were 8.77, 4.61, 14.59, 16.05 and 27.98 μg mL−1, respectively. However, the biosynthesized AgNPs revealed poor inhibition activities for the growth of E. coli and S. aureus. These results confirmed that the Sea Buckthorn could be a low-cost, nontoxic and eco-friendly natural resource for the synthesis of AgNPs, which might be useful for the development of new alternative antioxidant and anticancer agents in biomedicine.
研究领域:
纳米技术
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生物医学工程
·
药理学
·
植物科学
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癌症研究
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2023
·
IF 5
Chen Zhang,Zheng Jin,Yuhong Lin,Yiyu Wang,Kai Zhao
Doxorubicin (DOX) is considered one of the most effective chemotherapy drugs and is used as a first-line drug for many cancers. However, it has shown serious side effects such as cardiotoxicity and colonic ulcers , which limit its clinical use. Targeted delivery to tumor cells by nanocarriers or decreasing DOX dosage is considered to be an effective way to reduce the toxic and side effects of DOX on normal human tissues. In this paper, the mannose-functionalized N-2-HACC nanoparticles (MN NPs) loaded with DOX and Indocyanine Green (ICG) (DOX/ICG@MN NPs) were synthesized by the ion-crosslinking method, which were used for the in vitro targeted photothermal and chemical therapy. The results of FT-IR, particle size analysis, and SEM showed that ICG and DOX were successfully loaded, and DOX/ICG@MN NPs had great dispersibility and size. The results of the cell safety test showed that MN NPs had good safety. The photothermal stability tests revealed that the ICG in DOX/ICG@MN NPs had excellent thermal stability and photothermal conversion efficiency than the free ICG. The DOX release of DOX/ICG@MN NPs is pH-responsive, which promoted the effective release in slightly acidic environments at the tumor site. Owing to the specific targeting ability of mannose , DOX/ICG@MN NPs could be effectively uptake into HCT116 cells. In the presence of Near-Infrared irradiation (NIR), DOX/ICG@MN NPs exhibited synergistic treatment effects against tumor cells, which could significantly reduce the dosage of DOX and reduce the toxic side-effects on normal tissues. Therefore, this co-delivery system is considered to have significant potential for targeting tumors and chemo-photothermal therapy.
研究领域:
药学
·
纳米技术
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癌症治疗
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
·
2019
·Vol. 108
·期 1
·30-38
·
IF 3.221
Rui Ma,Zhen-Gang Ma,Jin-Lai Gao,Yu Tai,Lan-Jun Li,Hai-Bin Zhu,Li Li,De-Li Dong,Zhi-Jie Sun
Niclosamide is an antihelminthic drug. Recent studies show that niclosamide exerts antitumor activity through inhibiting multiple signals including Wnt/β-catenin, mTORC1, signal transducer and activator of transcription 3, NF-κB, notch signals; however, the insolubility and poor bioavailability limits its potential clinic use, the aim of the present work is to synthesize an injectable pegylated niclosamide (polyethylene glycol-modified niclosamide) and investigate its antitumor activity in vitro and in vivo. The pegylated niclosamide (mPEG5000-Nic) was synthesized and the chemical structure was identified by Fourier transform infrared spectra and 1 H nuclear magnetic resonance spectra. The antitumor activity was evaluated in CT26 and HCT116 colon cancer cells in vitro and nude mouse xenograft model of CT26 cells in vivo. The water solubility of niclosamide in mPEG5000-Nic was significantly increased. Niclosamide could be released from mPEG5000-Nic nanoparticles in PBS solution. mPEG5000-Nic inhibited the cell viability of CT26 and HCT116 cells in vitro. No animal death was observed in mice with intraperitoneal injection of mPEG5000-Nic (equivalent to 1000 mg/kg niclosamide) within 24 hr, indicating that mPEG5000-Nic was less toxic. In nude mouse, xenograft model of CT26 colon carcinoma, intraperitoneal injection of mPEG5000-Nic (equivalent to niclosamide 50 mg/kg) inhibited tumor growth but had no effect on animal body weight and heart, liver, kidney, and lung weight in vivo. Meanwhile, in the same model, intraperitoneal injection of the positive clinic drug 5-fluorouracil not only inhibited the tumor growth, but also reduced the animal body weight. Our study demonstrates that pegylated niclosamide is novel niclosamide delivery system with clinical perspective for cancer therapy.
研究领域:
药理学
·
肿瘤学
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药物递送系统
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Pharmaceutics
·
2024
·Vol. 16
·期 4
·512
·
IF 4.9
Junhong Ling,Yingying Cai,Haozhan Feng,Zhen Liu,Xiao-kun Ouyang
Disulfiram (DSF) degrades to diethyldithiocarbamate (DTC) in vivo and coordinates with copper ions to form CuET, which has higher antitumor activity. In this study, DSF@CuMSN-PDA nanoparticles were prepared using mesoporous silica with copper ions, DSF as a carrier, and polydopamine (PDA) as a gate system. The nanoparticles selectively released CuET into tumor tissue by taking advantage of the tumor microenvironment, where PDA could be degraded. The release ratio reached 79.17% at pH 5.0, indicating pH-responsive drug release from the nanoparticles. The PDA-gated system provided the nanoparticles with unique photothermal conversion performance and significantly improved antitumor efficiency. In vivo, antitumor experiments showed that the designed DSF@CuMSN-PDA nanoparticles combined with near-infrared light (808 nm, 1 W/cm2) irradiation effectively inhibited tumor growth in HCT116 cells by harnessing the combined potential of chemotherapy and photothermal therapy; a synergistic effect was achieved. Taken together, these results suggest that the designed DSF@CuMSN-PDA construct can be employed as a promising candidate for combined chemo-photothermal therapy.
研究领域:
纳米技术
·
药学
·
生物医学工程
·
癌症研究
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治疗诊断学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOID AND POLYMER SCIENCE
·
2020
·Vol. 298
·期 3
·303-312
·
IF 1.536
Gao Feng,Wang Qiang,Yang Xiaochun
Synthesis of amphiphilic poly( β -amino esters) (PBAE) was optimized by stepwise feeding of monomers (PBAE-(P-H)) compared with one-pot synthesis (PBAE-(P&H)) based on poly(ethylene glycol) diacrylate (PEGDA) and 1,6-hexanediol diacrylate (HDDA). Interestingly, optimized synthetic PBAE-(P-H) had smaller critical micelle concentration (CMC) of 6.6 μg/mL on average than one-pot synthetic PBAE-(P&H) (10.4 μg/mL). Nanoparticles were prepared based on PBAE-(P-H) and PBAE-(P&H), respectively. PBAE-(P-H) nanoparticles exhibited more narrow size distribution (average size, 105.3 nm; PDI, 0.103) than PBAE-(P&H) nanoparticles (average size, 117.8 nm; PDI, 0.233) demonstrated by dynamic light scattering and transmission electron microscopy. Afterward, PBAE-(P-H) and PBAE-(P&H) nanoparticles were selected to further investigate the properties including charge conversion and pH responsiveness. Doxorubicin (DOX) was encapsulated into nanoparticles. DOX release in vitro was enhanced as the decrease of pH value. Furthermore, DOX-loaded PBAE-(P-H) and PBAE-(P&H) nanoparticles exhibited enhanced cytotoxicity and cellular uptake against HCT116 cells compared with DOX under tumor microenvironment.
研究领域:
药学
·
纳米技术
·
材料科学
·
癌症研究
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）