MOLECULAR PHARMACEUTICS
·
2020
·
IF 4.321
Lan Cui,Xiayi Feng,Wentao Liu,Hao Liu,Qian Qin,Shuangxia Wu,Suqin He,Xinchang Pang,Dong Men,Chengshen Zhu
The surface charge of nanocarriers inevitably affects drug delivery efficiency; however, the cancer cell specificity, anti-inflammatory effects, and charge-reversal points remain to be further addressed in biomedical applications. The aim of this study was to comprehensively assess the cancer cell specificity of DOX-loaded mesoporous silica-chitosan oligosaccharide-carboxymethyl chitosan nanoparticles (DOX@MSNs-COS-CMC) in MCF-7 and HeLa cells, inhibit the production of inflammatory cytokines, and improve the drug accumulation in the tumor site. Intracellular results reveal that the retention time prolonged to 48 h in both HeLa and MCF-7 cells at pH 7.4. However, DOX@MSNs-COS-CMC exhibited a cell type-dependent cytotoxicity and enhanced intracellular uptake in HeLa cells at pH 6.5, due to the clathrin-mediated endocytosis and macropinocytosis in HeLa cells in comparison with the vesicular transport in MCF-7 cells. Moreover, Pearson’s correlation coefficient value significantly decreased to 0.25 after 8 h, prompting endosomal escape and drug delivery into the HeLa nucleus. After the treatment of MSNs-COS-CMC at 200 μg/mL, the inflammatory cytokines IL-6 and TNF-α level decreased by 70% and 80%, respectively. Tumor inhibition of DOX@MSNs-COS-CMC was 0.4 times higher than free DOX, alleviating cardiotoxicity and inflammation in the HeLa xenograft tumor model. Charge-reversible DOX@MSNs-COS-CMC could be a possible candidate for clinical therapy of cervical carcinoma.
研究领域:
药理学
·
肿瘤学
·
生物医学工程
·
纳米技术
✓ 已验证
DOI
PubMed
高影响因子
IEEE SENSORS JOURNAL
·
2025
·
IF 4.5
Jingqiu Chen,Qing Huang,Jing Huang,Tucan Chen,Lanpeng Guo,Yunong Zhao,Dandan Li,Wenjian Zhang,Huayao Li,Yang Zhang,Liang Hu,Huan Liu
The escalating demand for high-throughput and miniaturized biosensors has spurred significant advancements in biosensor chips. However, challenges remain in achieving high sensitivity and specificity in miniaturized devices. Herein, we construct a sensitive exosome biosensor based on quantum dots (QDs)-modified field effect transistor. PbS QDs were drop-coated onto the gate of a high electron mobility transistor (HEMT), followed by surface modification with CD63 antibodies (anti-CD63) through a ligand exchange strategy, and subsequent bovine serum albumin (BSA) blocking treatment. Exosomes with CD63 proteins enriched in the surface were isolated from MCF-7 breast cancer cell lines to serve as target analytes. The specific binding events between CD63 antigen and antibody capture exosomes onto the gate of HEMT, affecting the output current (ID). The synergy of the capacitance coupling effect of the modification layer and the intrinsic signal amplification capability of HEMT assists in significantly modulating the two-dimensional electron gas (2DEG), resulting in amplified ID. With constant gate voltage applied, the ID of the biosensor sensitively increases with exosome concentration within a wide range of 105-109 particles/mL at VD = 3.5 V, and the LOD is estimated to be 9 × 104 particles/mL. This exosome biosensor demonstrates its potential for clinical applicability and paves the way for the development of miniaturized exosome biosensor chips.
研究领域:
生物传感器
·
纳米技术
·
癌症诊断
·
生物电子学
·
微流控技术
✓ 已验证
产品关联
DOI
高影响因子
PLoS One
·
2013
·Vol. 8
·期 9
·e76544
·
IF 3.73
Qiaofeng Jin,Zhiyong Wang,Fei Yan,Zhiting Deng,Fei Ni,Junru Wu,Robin Shandas,Xin Liu,Hairong Zheng
A novel cationic microbubble (MB) for improvement of the DNA loading capacity and the ultrasound-mediated gene delivery efficiency has been developed; it has been prepared with commercial lipids and a stearic acid modified polyethylenimine 600 (Stearic-PEI600) polymer synthesized via acylation reaction of branched PEI600 and stearic acid mediated by N, N'-carbonyldiimidazole (CDI). The MBs’ concentration, size distribution, stability and zeta potential (ζ-potential) were measured and the DNA loading capacity was examined as a function of the amount of Stearic-PEI600. The gene transfection efficiency and cytotoxicity were also examined using breast cancer MCF-7 cells via the reporter plasmid pCMV-Luc, encoding the firefly luciferase gene. The results showed that the Stearic-PEI600 polymer caused a significant increase in magnitude of ζ-potential of MBs. The addition of DNA into cationic MBs can shift ζ-potentials from positive to negative values. The DNA loading capacity of the MBs grew linearly from (5±0.2) ×10 −3 pg/µm 2 to (20±1.8) ×10 −3 pg/µm 2 when Stearic-PEI600 was increased from 5 mol% to 30 mol%. Transfection of MCF-7 cells using 5% PEI600 MBs plus ultrasound exposure yielded 5.76±2.58×10 3 p/s/cm 2 /sr average radiance intensity, was 8.97- and 7.53-fold higher than those treated with plain MBs plus ultrasound (6.41±5.82) ×10 2 p/s/cm 2 /sr, (P<0.01) and PEI600 MBs without ultrasound (7.65±6.18) ×10 2 p/s/cm 2 /sr, (P<0.01), respectively. However, the PEI600 MBs showed slightly higher cytotoxicity than plain MBs. The cells treated with PEI600-MBs and plain MBs plus ultrasound showed 59.5±6.1% and 71.4±7.1% cell viability, respectively. In conclusion, our study demonstrated that the novel cationic MBs were able to increase DNA loading capacity and gene transfection efficiency and could be potentially applied in targeted gene delivery and therapy.
研究领域:
生物医学工程
·
基因治疗
·
超声技术
·
癌症研究
✓ 已验证
DOI
PubMed
高影响因子
CHEMISTRY OF NATURAL COMPOUNDS
·
2025
·
IF 0.9
Wang Yong,Wang Wei,Liu Li-Na,Wei Dong-Lin,Liu Cong-Jun,Wei Shang-Hua,Gao Song,Yu Shu-Ping,Yao Ning,Wang Yu-Fei
A series of abietic acid derivatives modified with a triazole moiety at the C-18 position were synthesized using Huisgen 1,3-dipolar cycloaddition reaction of 18-azidoabietane with alkynes. The antitumor activity of the synthesized compounds was investigated through human cervical cancer cells (HeLa), human breast cancer cells (MCF-7) and human renal epithelial cells (HEK-293T). The outcome indicated that compounds 5e , 5f , 5j exhibited positive inhibitory activity against the tested tumor cell lines. In particular, the IC 50 value for the inhibitory activity of compound 5e against human breast cancer cells (MCF-7) was 11.2 μmol/L.
研究领域:
药物化学
·
有机合成
·
肿瘤药理学
·
天然产物衍生物
✓ 已验证
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2017
·
IF 7.504
Ye Zhang,Congjun Zhang,Jing Chen,Li Liu,Mengyue Hu,Jun Li,Hong Bi
Multidrug resistance (MDR) has been recognized as a major obstacle to successful chemotherapy for cancer in the clinic. In recent years, more and more nanoscaled drug delivery systems (DDS) are constructed to modulate drug efflux protein (P-gp) and deliver chemotherapeutic drugs for overcoming MDR. Among them, d-α-tocopheryl polyethylene glycol succinate (TPGS) has been widely used as a drug carrier due to its capability of inhibiting overexpression of P-gp and good amphiphilicity favorable for improving permeation and long-circulation property of DDS. In the present work, a novel kind of mitochondria-targeting nanomicelles-based DDS is developed to integrate chemotherapeutics delivery with fluorescence imaging functionalities on a comprehensive nanoplatform. The mitochondria-targeting nanomicelles are prepared by self-assembly of triphenylphosphine (TPP)-modified TPGS and fluorescent carbon quantum dots (CQDs) in an n-hexane/H2O mixed solution, named CQDs-TPGS-TPP. Notably, although the drug loading content of doxorubicin (DOX) in the as-prepared nanomicelles is as low as 3.4%, the calculated resistant index (RI) is greatly decreased from 66.23 of free DOX to 7.16 of DOX-loaded nanomicelles while treating both parental MCF-7 cells and drug-resistant MCF-7/ADR cells. Compared with free DOX, the penetration efficiency of DOX-loaded nanomicelles in three-dimensional multicellular spheroids (MCs) of MCF-7/ADR is obviously increased. Moreover, the released DOX from the nanomicelles can cause much more damage to cells of drug-resistant MCs. These results demonstrate that our constructed mitochondria-targeting nanomicelles-based DDS have potential application in overcoming MDR of cancer cells as well as their MCs that mimic in vivo tumor tissues. The MDR-reversal mechanism of the DOX-loaded CQDs-TPGS-TPP nanomicelles is also discussed.
研究领域:
药学
·
纳米技术
·
癌症研究
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Cell and Developmental Biology
·
2022
·
IF 6.081
Deng Changping,Hu Fabiao,Zhao Zhangting,Zhou Yiwen,Liu Yuping,Zhang Tong,Li Shihui,Zheng Wenyun,Zhang Wenliang,Wang Tianwen,Ma Xingyuan
Quantitative analysis and regulating gene expression in cancer cells is an innovative method to study key genes in tumors, which conduces to analyze the biological function of the specific gene. In this study, we found the expression levels of Survivin protein (BIRC5) and P-glycoprotein (MDR1) in MCF-7/doxorubicin (DOX) cells (drug-resistant cells) were significantly higher than MCF-7 cells (wild-type cells). In order to explore the specific functions of BIRC5 gene in multi-drug resistance (MDR), a CRISPR/Cas9-mediated knocking-in tetracycline (Tet)-off regulatory system cell line was established, which enabled us to regulate the expression levels of Survivin quantitatively (clone 8 named MCF-7/Survivin was selected for further studies). Subsequently, the determination results of doxycycline-induced DOX efflux in MCF-7/Survivin cells implied that Survivin expression level was opposite to DOX accumulation in the cells. For example, when Survivin expression was down-regulated, DOX accumulation inside the MCF-7/Survivin cells was up-regulated, inducing strong apoptosis of cells (reversal index 118.07) by weakening the release of intracellular drug from MCF-7/Survivin cells. Also, down-regulation of Survivin resulted in reduced phosphorylation of PI3K, Akt, and mTOR in MCF-7/Survivin cells and significantly decreased P-gp expression. Previous studies had shown that PI3K/Akt/mTOR could regulate P-gp expression. Therefore, we speculated that Survivin might affect the expression of P-gp through PI3K/Akt/mTOR pathway. In summary, this quantitative method is not only valuable for studying the gene itself, but also can better analyze the biological phenomena related to it.
研究领域:
癌症生物学
·
分子生物学
·
基因工程
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2019
·
IF 3.973
Si Sun,Nihad Cheraga,Han-Ning Jiang,Qian-Ru Xiao,Peng-Cheng Gao,Yang Wang,Ying-Ying Wei,Xiao-Wei Wang,Yong Jiang
A variety of three-dimensional DNA assemblies have been proposed as drug carriers owing to their good biocompatibility and easy fabrication. In this study, inspired by the structure of cockleburs, a novel aptamer-tethered DNA assembly was developed for effective targeted drug delivery. The Apt-nanocockleburs were fabricated via a facile process of DNA base pairing: four complementary DNA single strands, including one aptamer-ended strand and three sticky-end strands, were applied to pair with each other. The main body of the nanocockleburs can load doxorubicin (Dox) whilst the covered aptamer spines bind to the target MCF-7 cells. The self-assembled Apt-nanocockleburs exhibit higher cell uptake as well as increased cytotoxicity to MCF-7 cells than DNA nanocockleburs without aptamers. This study provided a DNA constructing platform to produce new drug carriers with high selectivity for cancer targeted drug delivery.
研究领域:
纳米技术
·
药学
·
生物医学工程
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2024
·Vol. 28
·期 16
·e70032
·
IF 4.3
Qinbing Xue,Bing Wang,Jie Feng,Chaoyu Li,Miao Yu,Yan Zhao,Zheng Qi
Breast cancer (BC) is one of the most common types of cancer among women worldwide. Lycorine ( Lycoris radiata ), a small molecule derived from the traditional Chinese herb Amaryllidaceae plants, has appeared potential effect on inhibiting the growth of cancer cells and inducing apoptosis in various types of cancer with minor side effects. To discuss the therapeutic effects and molecular mechanisms of lycorine on BC established by lycorine-treated S180 tumour-bearing mice in vivo. Furthermore, both the mitotic and microtubule assembly dynamics genes were performed by qPCR assays, and the protein expression associated with mitotic arrest was investigated by western blot. Lycorine was demonstrated to reduce sarcoma growth of S180 tumour-bearing mice and inhibit the proliferation of MCF-7 cells in concentration-dependent manner. Moreover, lycorine induced M phase cell cycle arrest via interfering with the mitotic apparatus regulated the expression of 20 genes and 15 proteins in cell cycle progression. Furthermore, this study confirmed that the potential effect of lycorine on BC might be mediated by cell cycle arrest in M phase for the first time. These results would be the consequence of exploitation of lycorine as a potential drug for BC therapy, however further preclinical and clinical studies are still needed.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
中药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2019
·
IF 3.973
Qin-Qin Gao,Chuan-Min Zhang,En-Xia Zhang,Hui-Ying Chen,Yu-Hong Zhen,Shu-Biao Zhang,Shu-Fen Zhang
As zwitterionic polymers show great promise in drug delivery, hyaluronic acid (HA) was deacetylated and grafted with dodecylamine to prepare a pH-sensitive zwitterionic polymer dHAD used as a carrier for antitumor drugs. The polymer was negatively charged at pH 7.4 and became positive at pH 6.2. In vitro delivery of DOX against MCF-7 cells showed that the blank micelle dHAD had low cytotoxicity and the dHAD-DOX micelles could greatly prohibit the growth of the MCF-7 cells. In addition, the dHAD-DOX micelles had higher cellular uptake, indicating that the micelles were rapidly internalized into the cells via CD44 receptor-mediated endocytosis. The in vivo delivery of DOX to tumor-bearing mice confirmed that the dHAD-DOX micelles greatly inhibited the tumor growth and significantly reduced systemic toxicity of DOX. These results demonstrated that biocompatible pH-responsive zwitterionic dHAD micelles are promising carriers for the delivery of DOX.
研究领域:
药剂学
·
生物医学工程
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2017
·
IF 3.756
Yue Yang,Xiaoyu Lu,Qi Liu,Yu Dai,Xiaojie Zhu,Yanli Wen,Jiaqiu Xu,Yang Lu,Di Zhao,Xijing Chen,Ning Li
Combination therapy with two drugs and nanoparticle-based drug delivery systems are widely applied to reduce the adverse effects of traditional treatment by chemotherapeutic drugs. Palmitoyl ascorbate (PA) as a lipophilic derivative of ascorbic acid shows the advantages in cancer treatment. The aim of the study was to prepare a doxorubicin (DOX) and PA co-loaded liposome to synergistically treat tumor and effectively alleviate the toxicity caused by DOX. The effects were evaluated by in vitro and in vivo studies. The liposomes (weight ratio of DOX to PA = 1:20, DOX 1 /PA 20 -LPs) exhibited the strongest synergistic effects, combination index was 0.38, 0.56, and 0.05 in MCF-7, HepG2, and A549 cells, respectively. In vitro cellular uptake study, the intercellular concentration of DOX in DOX 1 /PA 20 -LPs was 2.5-fold greater than DOX loaded liposome, and DOX 1 /PA 20 -LPs was taken in not only by macropinocytosis, but also by clathrin-mediated endocytosis. Intracellular distribution experiment showed that DOX 1 /PA 20 -LPs efficiently concentrated in the nucleus. In vivo studies indicated that co-encapsulated liposome not only showed the strongest antitumor ability by tumor growth suppression, but also significantly enhanced the safety by the change of body weight and reduced damages to other tissues (evidenced by histopathology study). These results indicated that DOX and PA co-delivery liposome successfully enhanced the anticancer efficacy and mitigated the toxicities of DOX, which displayed potential for clinical application with enhanced safety and efficacy.
研究领域:
药理学
·
肿瘤学
·
纳米技术
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL BIOCHEMISTRY
·
2014
·
IF 2.305
Guang-Gang Gao,Guo-Biao Xu,Jin-Lian Li,Ji-Wen Cui,Dong-Mei Wu,Hong-Bin Qiu
Using an ultrasensitive chemically reduced graphene oxide and ionic liquid modified glass carbon electrode (RGI–GCE), separated electrochemical signals of adenine and hypoxanthine in both human breast cancer (MCF-7) and mouse embryonic fibroblast (BALB/3T3) cells were observed. For the first time, low-level expression of purine bases in noncancerous BALB/3T3 cells can be electrochemically monitored. The metabolism of purine bases in carcinogen agent-contaminated BALB/3T3 cells was also investigated through the change of electrochemical signals ascribed to different purine bases, which opens a new electrochemical approach to the exploration of a low-level purine mechanism in noncancerous cells.
研究领域:
生物化学
·
医学检测
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2015
·Vol. 5
·期 27
·20890-20899
·
IF 3.84
Minghui Xu,Junmin Qian,Aili Suo,Weijun Xu,Rongrong Liu,Hongjie Wang
Combination of chemotherapy and small interfering RNA (siRNA)-based therapy has emerged as a promising approach for cancer treatment with the synergistic effect. In this study, a novel terpolymer methoxy poly(ethylene glycol)-block-poly(N,N-dimethylaminopropyl methacrylamide)-block-poly(acrylhydrazine) (mPEG-b-PDMAPMA-b-PAH) with a disulfide linkage between mPEG and PDMAPMA blocks was developed for the intracellular targeted co-delivery of adriamycin and P-gp siRNA. The terpolymer was synthesized by sequential reversible addition–fragmentation chain transfer (RAFT) polymerization of N,N-dimethylaminopropyl methacrylamide and N-tert-butoxycarbonyl-N′-acryl hydrazine (Boc-acrylhydrazine) in the presence of a PEGylated macro-RAFT agent, followed by Boc-deprotection. The terpolymer could chemically conjugate adriamycin via an acid-cleavable hydrazone bond and simultaneously condense the negatively charged siRNA through electrostatic interactions at an N/P ratio of 2. The resultant adriamycin-conjugated nanoparticles/siRNA complexes (ADR-NPs/siRNA complexes) showed a spherical morphology and had an average diameter of 186 nm. The release profiles of the two payloads from the ADR-NPs/siRNA complexes exhibited a pH/reduction dual-dependent sustained release behavior. The ADR-NPs/siRNA complexes could simultaneously deliver adriamycin and siRNA efficiently into MCF-7/ADR cells and significantly inhibit their growth in a synergistic fashion. All the results indicated that the terpolymer mPEG-b-PDMAPMA-b-PAH could serve as a potential vehicle for the combination of chemotherapy and gene therapy.
研究领域:
药学
·
纳米技术
·
癌症研究
·
聚合物化学
·
药物递送系统
✓ 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）