Microsystems & Nanoengineering
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2024
·Vol. 10
·期 1
·1-12
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IF 7.3
Ma Yanmei,Hu Weikang,Hu Jian,Ruan Muyang,Hu Jie,Yang Ming,Zhang Yi,Xie Hanhan,Hu Chengzhi
Living cells can rapidly adjust their metabolic activities in response to external stimuli, leading to fluctuations in intracellular temperature and reactive oxygen species (ROS) levels. Monitoring these parameters is essential for understanding cellular metabolism, particularly during dynamic biological processes. In this study, we present a bifunctional nanoprobe capable of simultaneous measurement of ROS levels and temperature within single cells. The nanoprobe features two individually addressable nanoelectrodes, with platinum (Pt) and nickel (Ni) coatings on both sides. At the tip, these two metal layers form a nano-thermocouple, enabling precise intracellular temperature measurements, while the Pt layer facilitates selective ROS detection. This dual functionality allows for real-time monitoring of cellular responses during synergistic chemo-photothermal therapy of cancer cells and zebrafish embryos subjected to mitochondrial toxic stress. Our results demonstrate that the nanoprobe effectively measures increases in temperature and ROS levels in HeLa cells undergoing chemo-photothermal therapy, as well as in chemically stimulated zebrafish embryos. By providing detailed analysis of submicrometer-scale temperature and ROS variations within living cells, this nanoprobe offers valuable insights into cellular processes and holds promise for early disease detection and drug development.
研究领域:
生物物理学
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细胞生物学
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纳米技术
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癌症研究
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发育生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Yuping Wei,Man Zhang,Pengfei Jiao,Xin Zhang,Ganggang Yang,Xia Xu
In our pervious study, a dual-functional peptide R7 was developed to form a complex with paclitaxel (PTX) for enhancement of PTX translocation. However, because of the unstable noncovalent bond between R7 and PTX, PTX redistributed after the introduction of heparin, leading to R7-PTX complex dissociation, further causing less PTX penetration than expected. Thus, a novel positive CPP carrier of P9 was developed to improve CPP-PTX affinity via a double-proline (Pro, P) hairpin tail and enhance PTX translocation through the reduction of translocation energy barrier, confirmed by the MM-PBSA analysis and umbrella sampling simulation. Cellular uptake study reveals that P9 can quickly translocate into the HeLa cells within 1 min and exhibits no noticeable cytotoxicity. Compared to R7, P9 is able to help PTX translocation, leading to a remarkable increase in the intracellular concentration of PTX, eventually resulting in a significant loss in tumor cell viability. In vivo experiments demonstrate that a vein injection of P9-PTX complex dramatically inhibits tumor growth. Our study provides a novel perspective for designing CPP-facilitated drug carrier to enhance antitumor efficiency.
研究领域:
药学
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生物技术
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癌症研究
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2018
·
IF 3.997
Jing Zhang,Biao Shen,Liqun Chen,Lingdong Chen,Yangsheng Meng,Jie Feng
A multifunctional envelope-type mesoporous silica nanoparticle (MSN) was delicately designed for subcellular co-delivery of drug and therapeutic peptide to tumor cells. Firstly, a kind of cell apoptosis peptide (KLAKLAK) 2 (KLA) was anchored on surface of MSN via disulfide bond to obtain MSN-SS-KLA. Subsequently, anticancer drug doxorubicin hydrochloride (DOX) was loaded into the pores of MSN-SS-KLA. Then, the drug loaded MSN-SS-KLA (DOX@MSN-SS-KLA) was further coated with bovine serum albumin (BSA) to obtain a biological media stable MSN based drug delivery system (DDS), DOX@MSN-SS-KLA/BSA, for cancer synergetic therapy. The results show that stability of the DOX@MSN-SS-KLA/BSA is much better than that of DOX@MSN-SS-KLA and it could keep well dispersed in serum for more than 24 h. After accumulating at tumor site by EPR effect, the DOX@MSN-SS-KLA/BSA could be effectively phagocytosed by HeLa cells and release apoptotic peptide KLA as well as DOX simultaneously responding to reductive stimulus inside the cells. In vitro cell experiment results show that the DOX@MSN-SS-KLA/BSA complex exhibits much better inhibition on HeLa cells compared with pure DOX, indicating that co-delivery of KLA and DOX is expected to achieve synergetic therapy of cancer.
研究领域:
纳米技术
·
药学
·
癌症研究
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of the American Chemical Society
·
2019
·
IF 14.695
Wei Wang,Zhiguang Wu,Xiankun Lin,Tieyan Si,Qiang He
We report an ultrasound-driven gold-nanoshell-functionalized polymer multilayer tubular nanoswimmer that can photomechanically perforate the membrane of a cancer cell by assistance of near-infrared (NIR) light. The nanoswimmers were constructed by a template-assisted layer-by-layer technique and subsequent functionalization of Au nanoshells inside the big opening. The nanoswimmers exhibit efficient and controllable movement toward target cells through the manipulation of the acoustic field. Next, the nanoswimmers with end-on attachment onto the HeLa cells achieve the poration of the cell membrane within 0.1 s under the irradiation of NIR light. The experimental and theoretical results suggest that the instantaneous photothermal effect provides enough photomechanical force to open the cell membrane. Such NIR-light-assisted nanoswimmers-enabled cell membrane poration possesses various advantages including active targeting, short time, and precision in single cells that conventional chemical and physical cell poration techniques could not achieve and, thus, provides considerable promise in a variety of biomedical applications such as gene delivery and artificial insemination.
研究领域:
生物医学工程
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纳米技术
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细胞生物学
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治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2019
·
IF 3.414
Bin Xie,Yuan-Yuan Lu,Zhuo-Hui Luo,Zhao Qu,Chun-Ge Zheng,Xin-An Huang,Hong-Yan Zhou,Ying-Jie Hu,Xiao-Ling Shen
Ethnopharmacological relevance Marsdenia tenacissima (Roxb.) Wight et Arn is a vine distributed in southwest area of China and used in folk medicine for treatment of tumors. Recent decades of studies on this plant reveal its synergistic effects with certain anticancer drugs in cancer therapy. In our previous study, an extract ETA which contains total aglycones made from M. tenacissima significantly enhanced antitumor activity of paclitaxel in tumor-bearing mice. However, the effective constituents in ETA and the underlying mechanisms remain unclear. Aim of the study Reveal the active components in ETA as well as the molecular mechanism in enhancing antitumor efficacy of paclitaxel. Material and methods Main constituents in ETA were purified by chemical methods. Effects of the purified constituents on metabolic activity of CYP450 enzymes were evaluated in human liver microsomes. Ability of the constituents to enhance antitumor activity of paclitaxel were investigated in nude mice bearing HeLa tumors. Pharmacokinetic study was performed in SD rats . Molecular docking was carried out for investigation of drug-protein interactions. Results Three main C 21 steroidal aglycones, 11α- O -tigloyl-12β- O -acetyl-tenacigenin B ( MT1 ), 11α- O -2-methylbutanoyl-12β- O -tigloyl-tenacigenin B ( MT2 ) and 11α- O -2-methylbutanoyl-12β- O -acetyl-tenacigenin B ( MT3 ), together with tenacigenin B ( MT4 ) was prepared from ETA. Among them, MT1 , MT2 and MT3 strongly inhibit the metabolic activity of CYP3A4 . MT2 also showed inhibitory effects on CYP2C8 , CYP2B6 and CYP2C19 . In HeLa tumor xenografts, MT1 , MT2 and MT3 (30 mg/kg) did not affect tumor growth themselves, but significantly enhanced paclitaxel-induced growth inhibition. In addition, coadministration of MT2 with paclitaxel resulted in significant reduction of liver CYP2C8. In pharmacokinetic study, MT2 significantly increased the blood concentration of paclitaxel with increased AUC value by 2.2–5.3 folds. Molecular docking analysis suggested hydrophobic interaction modes of tenacigenin B derivatives with CYP3A4, and also the essential roles of the C-11 and C-12 ester groups for effective interaction with CYP3A4. Conclusion Our study proves that, 11α- O -tigloyl-12β- O -acetyl-tenacigenin B, 11α- O -2-methylbutanoyl-12β- O -tigloyl-tenacigenin B and 11α- O -2-methylbutanoyl-12β- O -acetyl-tenacigenin B, which are the main constituents of ETA, are active inhibitors of CYP3A4 with potential to increase therapeutic efficacy of anticancer drugs that are substrates of CYP3A4. Tenacigenin B derivatives with C-11 and C-12 ester group substitutions, or at least a large part of them, are active components in ETA and M. tenacissima to enhance in vivo antitumor efficacies of paclitaxel.
研究领域:
药理学
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肿瘤学
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民族药理学
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生物化学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2018
·
IF 3.412
Jingjing Luo,Xiaofeng Meng,Jianyu Su,Hang Ma,Wen Wang,Liming Fang,Huade Zheng,Yexia Qin,Tianfeng Chen
15,16-Dihydrotanshinone I (DI), a natural compound isolated from a traditional Asian functional food Salvia Miltiorrhiza Bunge, is known for its anticancer activity. However, poor solubility of DI limits its desirable anticancer application. Herein, polylactic-co-glycolic acid (PLGA) was functionalized with polyethylene glycol (PEG) and biotin to form copolymers PEG-PLGA (PPA) and biotin-PEG-PLGA (BPA). DI was encapsulated in copolymers PPA and BPA to obtain DI-PPA-NPs (NPs = nanoparticles) and DI-BPA-NPs, respectively. The particle size and its distribution, encapsulation efficiency, and in vitro releasing capacity of DI-BPA-NPs were characterized by biophysical methods. MTT assay was used to evaluate the antiproliferative activity of free DI, DI-PPA-NPs, and DI-BPA-NPs in human cervical cancer Hela cells. DI-BPA-NPs showed the highest cytotoxicity on Hela cells with an IC50 value of 4.55 ± 0.631 μM, while it was 8.20 ± 0.849 and 6.14 ± 0.312 μM for DI and DI-PPA-NPs in 72 h, respectively. The superior antiproliferative activity was supported by the fact that DI-BPA-NPs could be preferentially internalized by Hela cells, owing to their specific interaction between biotin and overexpressed biotin receptors. In addition, DI-BPA-NPs effectively inhibited Hela cell proliferation by inducing G2/M phase cycle arrest and decreasing the intracellular reactive oxygen species (ROS) level by 31.50 ± 2.29% in 5 min. In summary, DI-BPA-NPs shows improved antiproliferative activity against human cervical cancer as comparing with free DI, demonstrating its application potential in cancer therapy.
研究领域:
药理学
·
纳米技术
·
肿瘤学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2018
·
IF 8.173
Lei Wang,Tianjiao Meng,Guangshun Yu,Shasha Wu,Jingjing Sun,Huixian Jia,Huan Wang,Xinjian Yang,Yufan Zhang
An electrochemical biosensor was designed for the determination of telomerase activity using an enzyme-free, PCR-free, and convenient electrochemical strategy. In this work, the electrochemical biosensor was constructed through the functionalization of Au nanorods with a carboxylic group (AuNRs-3) and subsequent immobilization with capture DNA (cDNA) for sensing telomerase activity. Upon telomerase triggered extension, the telomerase activity is related to the amount of the adsorbed electrocatalyst , leading to the different electrochemical signals for readout. Integrating with the efficient electrocatalysis of AuNRs-3-cDNA towards oxidation of acetaminophen, the prepared biosensor exhibits a wide dynamic correlation of telomerase activity from 1 × 10 2 to 1.04 × 10 7 HeLa cells mL −1 with a sensitivity of 2.68 HeLa cell mL −1 and the limit of detection was calculated to be 52.81 HeLa cells mL −1 under the optimal experimental conditions. Furthermore, the application of this electrochemical biosensor would provide the great potential for analysis of telomerase activity, revealing a powerful platform for early diagnosis of cancers.
研究领域:
生物传感器
·
电化学
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癌症诊断
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纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2022
·
IF 16.744
Yi Zhang,Da Luo,Yin Zhang,Qi-Hai Zhang,Qing-Yuan Ji,Shi-Kang Zhou,Shan Huang,Li-li Li,Feng Lu,Wei-Feng Yao,Fang-Fang Cheng,Jun-Jie Zhu,Li Zhang
Upconversion nanoparticles (UCNPs) are promising materials for imaging biomolecules and predicting the progression of diseases, especially for tumors. However, conventional luminescence resonance energy transfer (LRET) based nanosensors remain challenging with complicated modification and unsatisfactory sensitivity. Herein, a sensing platform integrating confined emission effect and cycling amplification strategy into one substrate with high LRET efficiency and sensitivity has been developed for the in - vitro and in - vivo detection of microRNA-21. Washing UCNPs with hydrochloric acid was conducted for electrostatic absorption of 8–17 DNAzyme labeled with BHQ1 (8–17 DNAzyme-BHQ1) and complementary capturing template-aDNA3 complex (CPT-aDNA3) to form energy donor–acceptor pair (UCNPs-BHQ1) and capture miR-21. It not only avoids the complex modification procedure but also shortens the distance between the donor (UCNPs) and the acceptor (BHQ1). The quenching efficiency of 60.94 % was obtained. Targeted miR-21 could bind with CPT to release aDNA3 that can unlock 8–17 DNAzyme-BHQ1 to form aDNA3-DNAzyme-BHQ1 duplex. This aDNA3-DNAzyme-BHQ1 duplex owning -rA- group can be cleaved by Zn 2+ so that UCNPs restored green UCL emission because of the desorption of BHQ1. aDNA3 becomes dissociative again to trigger the next cycle. This [email protected] /CPT- aDNA3 achieved a wide linear range from 4 × 10 -14 M to 1 × 10 -8 M with a low limit detection of 31 fM for the sensitive detection of miR-21 in vitro . Furthermore, it was successfully applied to the real-time intracellular detection of miR-21 in HeLa cells and in - vivo monitoring of miR-21 expression in KS-01 treated tumor-bearing mouse. This proposed DNA-conjugated upconversion nanoamplicon provides new sights into monitoring of anti-cancer active ingredients efficacy and the progress evaluation of miRNA-related diseases.
研究领域:
纳米技术
·
生物医学工程
·
分子生物学
·
癌症研究
·
生物成像
✓ 已验证
产品关联
DOI
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2016
·
IF 7.476
Bing-Huan Huang,Zhi-Rong Geng,Xiao-Yan Ma,Cui Zhang,Zhi-Yang Zhang,Zhi-Lin Wang
Lysosomes in astrocytes and microglia can release ATP as the signaling molecule for the cells through ca 2+ -dependent exocytosis in response to various stimuli. At present, fluorescent probes that can detect ATP in lysosomes have not been reported. In this work, we have developed a new water-soluble cationic polythiophene derivative that can be specifically localized in lysosomes and can be utilized as a fluorescent probe to sense ATP in cells. PEMTEI exhibits high selectivity and sensitivity to ATP at physiological pH values and the detection limit of ATP is as low as 10 −11 M. The probe has low cytotoxicity, good permeability and high photostability in living cells and has been applied successfully to real-time monitoring of the change in concentrations of ATP in lysosomes though fluorescence microscopy . We also demonstrated that lysosomes in Hela cells can release ATP through Ca 2+ -dependent exocytosis in response to drug stimuli.
研究领域:
细胞生物学
·
神经科学
·
生物化学
✓ 已验证
DOI
PubMed
高影响因子
Science Bulletin
·
2016
·
IF 0
Bo-Ya Liu,Cong Wu,Xiao-Yan He,Ren-Xi Zhuo,Si-Xue Cheng
A facile self-assembly strategy to fabricate vitamin E-tocopheryl polyethylene glycol succinate (TPGS) based nanoparticles with a high drug loading level for co-delivery of multiple drugs was developed. To overcome multi-drug resistance, a chemotherapeutic agent (paclitaxel, PTX) and a drug resistance inhibitor (tariquidar, TQR) were co-loaded in the vitamin E-TPGS based nanoparticle to obtain TPGS/PTX/TQR nanoparticles. The sizes of mono-drug loaded TPGS/PTX nanoparticles and dual-drug loaded TPGS/PTX/TQR nanoparticles were below 150 nm with relatively narrow size distributions. The efficiencies of the drug delivery systems on tumor cells inhibition and reversal of drug resistance were evaluated in drug resistant cancer cells (MCF-7/ADR) as compared with nonresistant cells (HeLa). Due to the effective inhibition of the P-gp efflux by TQR, the dual-drug loaded nanoparticles exhibited significantly improved tumor cell inhibitory efficiency. To study the immunostimulatory effect, the effect of the drug delivery system on the production of IL-10, a cytokine related to tumor development, in the drug resistant cells was determined. After the treatment by the drug delivery systems, the concentration of IL-10 in the cell supernatant decreased. The multi-drug loaded vitamin E-TPGS nanoparticles for synergistic drug delivery have promising applications in reversal of drug resistance in tumor treatments.
研究领域:
药学
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纳米技术
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肿瘤学
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药物递送系统
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生物医学工程
✓ 已验证
产品关联
DOI
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2018
·
IF 5.091
Kuikui Zhang,Qi Zhao,Shirong Qin,Yang Fu,Runze Liu,Jinfang Zhi,Chongxin Shan
A multifunctional nanoplatform with simultaneous imaging and therapeutic capacities has been fabricated by covalently conjugating nanodiamonds (NDs) with upconversion NaYF 4 :Yb,Er nanoparticles (UCNPs). Green emission can be observed for the UCNP-NDs composites under 980 nm excitation, and in vitro imaging was carried out towards HeLa cells. The UCNP-NDs also shows good drug storage capability toward anticancer drug doxorubicin (Dox) and exhibits significant pH-dependent drug-release behavior. Dox-loaded UCNP-NDs shows higher therapy efficiency towards Hela cells than free Dox when the equivalent concentration of the Dox is more than 10 μg/mL. Thus, a favorable strategy may be provided to decrease the side effects of Dox, minimize drug dose, and improve its efficacy. These findings highlight the fascinating features of UCNP-NDs nanocomposites as upconversion fluorescence imaging contrast agents and doxorubicin loading carrier. In addition, this work may also provide a novel strategy for the design of multifunctional nanoplatforms.
研究领域:
生物医学工程
·
纳米技术
·
药学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2020
·
IF 7.182
Zhao Zhao,Mei Ji,Qianqing Wang,Nannan He,Yue Li
Off-target drug delivery, together with multidrug resistance (MDR), are two keys obstacles that account for the disappointing outcome in clinical chemotherapy of cancer. To solve these dilemmas, Herein, we constructed cancer cell membrane (CCM) modified silica (CS) nanoparticles (CCM/CS) to co-deliver Ca 2+ channel siRNA with doxorubicin (DOX) to construct a platform (CCM/CS/R-D) for the efficient therapy of cervical cancer. It was demonstrated that the optimal CCM/CS/R-D was spherical nanoparticles with size at 122.39 ± 4.69 nm and the surface charge of -27.76 ± 3.12 mV. In addition, the CCM/CS/R-D showed acid responsive drug release while high stability under physiological conditions with negligible hemolysis. The CCM/CS/R-D showed CCM mediated cellular uptake and efficient endosomal escape as well as siRNA transfection potential (comparable to that of PEI 25 K) on MDR cervical cancer cells (HeLa/DOX). Most importantly, the MDR of cancer cells was conquered through modulation of T-type Ca 2+ (Cav) channels. It was observed that the Cav channel siRNA could negatively regulate the level of cytosolic Ca 2+ concentration which triggered G0/G1 phase cell cycle arrest and elevated intracellular drug retention in HeLa/DOX cells without significantly affect the expression of P-glycolprotein (P-gp). The in vitro and in vivo experiments revealed that CCM/CS/R-D exerted greatly enhanced tumor targetability and therapeutic effect on HeLa/DOX, which was superior than CS/R-D or mono delivery system (CCM/CS/R or CCM/CS/D).
研究领域:
癌症研究
·
纳米医学
·
药理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）