JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Xi Wang,Guiquan Liu,Xueyu Pu,Tangjun Ren,Fan Zhang,MengJie Shen,Yan Zhu,Alexander Kros,Jian Yang
Drug resistance to chemotherapy in treating cancers becomes an increasingly serious challenge, which leads to treatment failure and poor patient survival. Drug-resistant cancer cells normally reduce intracellular accumulation of drugs by controlling drug uptake and promoting drug efflux, which severely limits the efficacy of chemotherapy. To overcome this problem, a membrane fused drug delivery system (MF-DDS) was constructed to treat cisplatin (DDP)-resistant lung cancer (A549-DDP) by delivering DDP via membrane fusion using a complementary coiled-coil forming peptides (CP 8 K 4 /CP 8 E 4 ). The lipopeptide CP 8 K 4 was pre-incubated firstly and decorated on the surface of A549-DDP cells, and then the cells interacted with the lipopeptide CP 8 E 4 modified on the lipid bilayer (LB) coated PLGA nanoparticles loading DDP (PLGA-DDP@LB-CP 8 E 4 ), leaded to the direct cytosolic DDP delivery and cancer cell death. Compared with free DDP, this MF-DDS achieved a 13.42-folds reduced IC 50 value of A549-DDP cells in vitro , and tumor size was down-regulated, showing only 1/5.26 of the original weight in vivo . Meanwhile, the anti-drug resistant mechanism was explored, where the MF-DDS inhibited the expression of efflux protein genes, including MRP1, MRP2, and ABCG2, leading to increased intracellular drug accumulations. Altogether, this MF-DDS effectively delivered DDP into DDP-resistant cancer cells, making it a promising and improved pharmacological therapeutic approach for drug-resistant tumor treatment.
研究领域:
肿瘤学
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药理学
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纳米技术
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2019
·
IF 3.926
Ya-Liang Zhang,Rong Yang,Lin-Ying Xia,Ruo-Jun Man,Yi-Chun Chu,Ai-Qin Jiang,Zhong-Chang Wang,Hai-Liang Zhu
Twenty-four 1,2-diarylbenzimidazole derivatives were designed, synthesized and biologically evaluated. It turned out that most of them were potential anticancer drugs. Among them, compound c24 showed the highest anti-tumor activity (GI 50 = 0.71–2.41 μM against HeLa, HepG2, A549 and MCF-7 cells), and low toxicity to normal cells (CC 50 > 100 μM against L02 cells). In the microtubule binding assay, c24 showed the most potent inhibition of microtubule polymerization (IC 50 = 8.47 μM). The binding ability of compound c24 to tubulin crystal was verified by molecular docking simulation experiment. Further studies on HepG2 and HeLa cells showed that compound c24 could cause mitotic arrest of tumor cells to G2/M phase then inducing apoptosis. To sum up, compound c24 is a promising microtubule assembly inhibitor.
研究领域:
药理学
·
癌症研究
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Analytical Methods
·
2019
·Vol. 11
·期 14
·1857-1867
·
IF 2.378
Qing He,Ruixi Li,Zhenwei Yuan,Habtamu Kassaye,Jinrong Zheng,Chen Wei,Fei Wang,Yuxin Yao,Lijuan Gui,Haiyan Chen
Cysteine (Cys) has emerged as a significant sensing target in recent years. Although a lot of biothiol probes have been developed and applied to cellular imaging through thiol-induced disulfide cleavage or Michael addition reactions, relatively few probes assessing Cys with high selectivity over glutathione (GSH) and homocysteine (Hcy) with near-infrared (NIR) fluorescence are capable of in vivo fluorescence imaging in biological systems. Herein, a NIR fluorescent turn-on probe for Cys monitoring in vivo was designed and synthesized. This probe demonstrated a rapid, tremendously selective detection process for Cys with remarkable NIR fluorescence enhancement (Ex: 600 nm, Em: 712 nm, ∼20 fold). In addition, this probe could be utilized to quantitatively detect Cys with a detection limit of 82 nM over a wide linear range (0.01–160 μM), fast response time (5 min) and low toxicity. Moreover, it was further demonstrated that this NIR fluorescent probe could be applied to detect Cys in living cells including L02, A549 and MCF-7 cell lines and different mouse models (tumor-bearing mouse model, hepatitis model and inflammatory model), revealing that this probe possesses great promise for further biological applications.
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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药学
✓ 已验证
产品关联
DOI
高影响因子
Nanoscale
·
2014
·Vol. 6
·期 15
·8535-8542
·
IF 6.739
Xiangyan Zhou,Marco Dorn,Jürgen Vogt,Daniel Spemann,Wei Yu,Zhengwei Mao,Irina Estrela-Lopis,Edwin Donath,Changyou Gao
Noble-metal nanoparticles (NPs) especially prepared from gold and silver have been combined on the surface of graphene to obtain graphene-based nanocomposites for novel functions in enhanced performance in bio-imaging, cancer detection and therapy. However, little is known about their cellular uptake, especially the intracellular quantity which plays a critical role in determining their functions and safety. Therefore, we prepared covalently conjugated GO/Au and GO/Ag composites by immobilizing Au and Ag nanoparticles on GO sheets pre-functionalized with disulfide bonds, respectively. The cellular uptake of these composites was quantitatively studied by means of an ion beam microscope (IBM) to determine the metal content in human lung cancer cells (A549 cells) and liver hepatocellular carcinoma cells (HepG2 cells). The cell uptake was also studied by inductively coupled plasma mass spectrometry (ICP-MS), which is one of the most sensitive techniques being applied to cell suspensions, for comparison. Toxicity, one of the consequences of cellular uptake of GO based composites, was studied as well. The potential toxicity mechanism was also suggested based on the results of intracellular quantification of the nanomaterials.
研究领域:
纳米技术
·
生物医学工程
·
毒理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2015
·
IF 3.65
Naxin Ma,Baohua Zhang,Jing Liu,Pei Zhang,Zhonghao Li,Yuxia Luan
A green and mild approach for the preparation of reduced graphene oxide (rGO) was proposed by using riboflavin-5′-phosphate sodium salt dihydrate as a reducing reagent and stabilizer without any other reagent. The fabricated nano-rGO was systematically evaluated for its application as nano-carrier for pH-sensitive drug delivery. The hemolytic toxicity test indicated the as-prepared nano-rGO had negligible hemolytic activity, which demonstrating its safety in drug delivery system. Doxorubicin hydrochloride (DOX) as a model drug was successfully attached onto the surface of nano-rGO via strong π–π stacking interaction. Compared with common carriers, the obtained DOX-loaded nano-rGO nanohybrid exhibited characteristics of high drug loading content, good stability, pH-sensitive and sustainable release of drugs. Cytotoxicity assay results suggested such nanohybrid exhibited effective cytotoxicity to MCF-7 and A549 cells by nonspecific endocytosis mechanism. Therefore, the present green fabricated rGO could be a good candidate as an ideal nano-carrier for drug delivery and controlled release.
研究领域:
材料科学
·
药学
·
纳米技术
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2024
·
IF 6.9
Sikai Deng,Weiwei Li,Qiyu Chen,Jianqun Shao,Junbo Zhang,Yuji Wang,Yinghuan Li
The mucus layer and intestine epithelium pose challenges to the bioavailability of orally administered paclitaxel (PTX). A novel P-glycoprotein inhibitor, (S)-2-decanoylamino-3-(1-naphthyl)propionyl-leucyl-valine (PgpI), was synthesized in this study. Its structure was characterized using 1 H NMR, 13 C NMR, ESI-MS and IR spectroscopies. The efficacy and in vivo toxicity of PgpI were comprehensively evaluated by R8-PEG@PLs&PgpI, i.e. , the oral combination of PgpI and octaarginine R8-PEG-DSPE modified PTX liposomes (R8-PEG@PLs), for lung cancer treatment. The joint forms between PgpI and R8-PEG@PLs were investigated and the affinity of PgpI for intestinal P-glycoprotein remained unaffected when combined externally with R8-PEG@PLs (R8-PEG@PLs&PgpI), compared to the diminished affinity for internal combination. The primary endocytic pathway for R8-PEG@PLs&PgpI in Caco-2 cells was the lipid raft, with increased percentage of macropinocytosis compared to unmodified PTX liposomes (PLs). The established physiology-based cellular kinetic models revealed that the net internalization rate of PTX was 2.3 times higher in R8-PEG@PLs&PgpI than in PLs, correlating with in vivo 2.2 times of antitumor rate. R8-PEG@PLs&PgpI may address the deficits of PLs in human lung A549 tumor-bearing mice due to the lower drug concentration than in normal mice. The external combination of R8-PEG@PLs&PgpI, offering maximal efficacy and security of PgpI, is promising for oral PTX delivery.
研究领域:
药学
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肿瘤学
·
药物递送系统
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Bioengineering & Translational Medicine
·
2021
·Vol. 7
·期 2
·e10290
·
IF 10.711
Fabiao Hu,Changping Deng,Yiwen Zhou,Yuping Liu,Tong Zhang,Peiwen Zhang,Zhangting Zhao,Hui Miao,Wenyun Zheng,Wenliang Zhang,Meiyan Wang,Xingyuan Ma
Regulation of the apoptotic pathway plays a critical role in inducing tumor cell death and circumventing drug resistance. Survivin protein is the strongest inhibitor of apoptosis found so far. It is highly expressed in several cancers and is a promising target for cancer therapy. However, clinical applications are limited by incomplete inhibition of survivin expression. Here, we present a novel strategy that extended the release of YM155 (an effective survivin inhibitor that works by inhibiting the activity of survivin promoter) and TATm-survivin (T34A) (TmSm) protein (survivin protein mutant with penetrating peptide, a potential anticancer protein therapeutic) via tumor matrix microenvironment-mediated ferritin heavy chain nanocages (FTH1 NCs), enabling significant inhibition of survivin activity at both transcript and protein levels. FTS (FTH1-matrix metalloproteinase-2-TmSm)/YM155 NC synthesis was easily scaled up, and these NCs could sequentially release TmSm protein through matrix metalloproteinase-2 and promote YM155 to enter the nucleus via transferrin receptor 1 (TfR1) binding, which increased the cytotoxicity and apoptosis of Capan-2 and A549 cells compared to that with individual drugs. Moreover, FTS/YM155 NCs enhanced drug accumulation at tumor sites and had a higher tumor inhibition rate (88.86%) than the compounds alone in A549 tumor-bearing mice. In addition, FTS/YM155 NCs exerted significant survivin downregulation (4.43-fold) and caspase-3 upregulation (4.31-fold) and showed better therapeutic outcomes without inducing organ injury, which highlights their promising future clinical application in precision therapy. This tumor microenvironment-responsive platform could be harnessed to develop an effective therapy via multilevel inhibition of cancer targets.
研究领域:
癌症生物学
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纳米技术
·
药学
·
分子生物学
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治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2017
·
IF 4.4
Lin Xi,Yan Shu-Zhen,Qi Shan-Shan,Xu Qiao,Han Shuang-Shuang,Guo Ling-Yuan,Zhao Ning,Chen Shuang-Lin,Yu Shu-Qin
Photodynamic therapy (PDT) has emerged as a potent novel therapeutic modality that induces cell death through light-induced activation of photosensitizer. But some photosensitizers have characteristics of poor water-solubility and non-specific tissue distribution. These characteristics become main obstacles of PDT. In this paper, we synthesized a targeting drug delivery system (TDDS) to improve the water-solubility of photosensitizer and enhance the ability of targeted TFR positive tumor cells. TDDS is a transferrin-modified Poly(D,L-Lactide-co-glycolide (PLGA) and carboxymethyl chitosan (CMC) nanoparticle loaded with a photosensitizer hypocrellin A (HA), named TF-HA-CMC-PLGA NPs. Morphology, size distribution, Fourier transform infrared (FT-IR) spectra, encapsulation efficiency, and loading capacity of TF-HA-CMC-PLGA NPs were characterized. In vitro TF-HA-CMC-PLGA NPs presented weak dark cytotoxicity and significant photo-cytotoxicity with strong reactive oxygen species (ROS) generation and apoptotic cancer cell death. In vivo photodynamic antitumor efficacy of TF-HA-CMC-PLGA NPs was investigated with an A549 (TFR positive) tumor-bearing model in male athymic nude mice. TF-HA-CMC-PLGA NPs caused tumor delay with a remarkable tumor inhibition rate of 63% for 15 days. Extensive cell apoptosis in tumor tissue and slight side effects in normal organs were observed. The results indicated that TDDS has great potential to enhance PDT therapeutic efficacy.
研究领域:
药学
·
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
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2022
·
IF 5.999
Jianbo Lin,Rujie Zheng,Liping Huang,Yuanrong Tu,Xu Li,Jianfeng Chen
Molecularly targeted drugs are flourishing in the clinical treatment of non-small cell lung cancer (NSCLC). However, the treatment of a single drug (such as Gefitinib (Geb)) had defects such as poor pharmacokinetics , insufficient drug delivery, and considerable toxic side effects, which greatly affect its therapeutic efficacy against NSCLC. To solve these issues, this study developed a new nanocomposite heterogeneous platform (MSNs@Ag@Geb-FA) that combined photothermal therapy and molecular targeted therapy. The high specific surface area empowered mesoporous silicon dioxide (SiO 2 ) heterostructure the ability to efficiently load Ag photothermal agents and anti-tumor drug Geb. Meanwhile, a favorable pH response (degradation of residual MnO 2 ) achieved the controlled release of Ag and Geb. Besides, the targeting and endocytosis properties of nano drugs were greatly improved through the modification of folic acid (FA). Both in vivo and in vitro experiments authenticated that this nanocomposite heterogeneous platform could effectively integrate the multiple tumor suppressor properties of Ag nanoparticles and cooperate with Geb to hasten A549 cell apoptosis, thereby achieving a favorable anti-tumor effect. This heterogeneous structure of the nanocomposite heterogeneous platform could provide an effective strategy for the treatment of NSCLC.
研究领域:
纳米技术
·
药学
·
癌症研究
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE
·
2022
·Vol. 57
·期 24
·11317-11331
·
IF 4.682
Hao Dule,Zhang Zheng,Cheng Yu,Cheng Long,Ji Yuanhui
An increasing number of studies have demonstrated that inflammation has a close correlation with multiple stages of tumor development, including tumor initiation, promotion, and migration. Cyclooxygenase-2 (COX-2), which is overexpressed in inflammation, has also been found to be overexpressed in several types of cancer. Some anti-inflammatory drugs have been shown to have potential effects on the inhibition of tumor pathogenesis and development. Among them, non-steroidal anti-inflammatory drugs (NSAIDs) play a role by inhibiting the overexpression of COX-2 with low price and few side effects. In this work, ibuprofen was linked to an amphiphilic polymer mPEG-PLA via disulfide bond to form a polymeric prodrug molecule with reductive sensitivity. The amphiphilic molecule can self-assemble into nanoparticles in an aqueous solution and encapsulate hydrophobic drug, doxorubicin, into the core. Electrostatic potential analysis and weak interaction analysis showed different weak interactions, including hydrogen bonds and π-π stackings, are the driving force of the formation of the complex system between doxorubicin and polymeric prodrug molecules. These quantitative calculations were helpful to understand the formation mechanism of prodrug polymeric carriers. Characterization methods such as TEM and DLS proved that mPEG-PLA- s -IHE/DOX (PDC/DOX) micelles had an excellent uniform nanostructure, and in vitro drug release experiments showed superior sustained-release and reductive environment-dependent release of this drug. More importantly, in vitro cytotoxicity and cell uptake studies showed that the PDC/DOX micelles induced apoptosis of A549 lung cancer cell lines. This study demonstrates the advantage of combining NSAIDs with chemotherapy agents in the treatment of lung cancer, which provides a feasible and novel polymer delivery system, and a reasonable explanation of formation mechanism. Graphical Abstract
研究领域:
药学
·
材料科学
·
癌症研究
·
纳米技术
✓ 已验证
产品关联
DOI
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2022
·
IF 4.831
Yu Hou,Jiawei Lin,Yichao Chen,Jianbin He,Zhe Su,Qinhua Zheng,Xiujuan Zhao,Xiaodan Lv,Xiuping Tang,Changren Zhou
Monitoring hydroxyl radical (•OH) fluctuation is of great importance to study some relative pathological processes and to predict early diagnosis of diseases. Efficient •OH-responsive fluorescent sensors based on carbon dots (CDs) have been reported, but most researches have focused on the new strategies for the synthesis and doping of the CDs. Herein, a kind of biomass CDs (F-CDs) with Flammulina velutipes ( F. velutipes ) as the carbon source was prepared by a one-step hydrothermal method without any additional modification. The prepared F-CDs have remarkable sensitivity and selectivity and there is a good linear relationship from 0 to 12 μM with a low detection limit of 95 nM for quantitative •OH assay. With excitation-independent emission, favourable biocompatibility and low toxicity, the F-CDs can penetrate cell membranes as •OH-responsive fluorescent sensors to detect intracellular •OH in A549 cells stimulated by phorbol 12-myristate 13-acetate (PMA) and successfully monitor the •OH concentration levels by the corresponding fluorescence change. Given the combined benefits of the green and eco-friendly approach, the F-CDs show promise as novel theranostics tools for early detection and treatment of related diseases.
研究领域:
化学
·
材料科学
·
生物材料
·
生物医学工程
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2023
·
IF 5
Dan Ma,Hai Zhang,Mao Zhao,An-ru Liao,Qian-rong Peng,Wen-wen Jiang,Min Yang
Combination therapy and the drug delivery in response to the tumor microenvironment can effectively improve the efficacy of anticancer therapy. Polymeric nanoparticles can increase the solubility of water-insoluble drugs and have been evaluated as carriers for anti-cancer drugs in several clinical trials . In this paper, zinc phthalocyanine-encapsulated with a boronate-linked polydopamine-poloxamers 407 nanoparticles were developed for pH response and reactive oxygen species (ROS) response release, as well as synergistic photothermal and photodynamic effects. These nanoparticles exhibited a favorable size of 75.02 ± 1.12 nm , stability within 28 days, pH and ROS release up to 57.29% within 84 h, and 73.5% inhibition of A549 cells at a concentration of 5 μg/mL. Overall, our work provides an effective strategy for the encapsulation of hydrophobic photosensitizers , combined PDT and PTT therapy.
研究领域:
纳米技术
·
癌症治疗
·
药物递送系统
·
生物医学工程
✓ 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）