BIOMATERIALS
·
2014
·
IF 8.312
Wantong Song,Zhaohui Tang,Dawei Zhang,Ying Zhang,Haiyang Yu,Mingqiang Li,Shixian Lv,Hai Sun,Mingxiao Deng,Xuesi Chen
There are two important obstacles for the currently applied anti-cancer drug delivery systems. One is the conflict between long-circulation and cellular uptake while the other one is the achievement of ideal anti-cancer efficacy. To solve these problems, we designed a polypeptide-based micelle system that combined the advantages of receptor mediated endocytosis and multi-drug delivery. Firstly, an amphiphilic PLG- g -Ve/PEG graft copolymer was prepared by grafting α-tocopherol (Ve) and polyethylene glycol (PEG) to poly( l -glutamic acid) (PLG). Then docetaxel (DTX) and cisplatin (CDDP) were co-loaded into the PLG- g -Ve/PEG micelles via hydrophobic and chelation effect. After that, the surface of the dual-drug-loaded micelles was decorated with an α v β 3 integrin targeting peptide c(RGDfK). The targeted dual-drug-loaded micelles showed synergistic cytotoxicity and enhanced internalization rate in mouse melanoma (B16F1) cells. In vivo tests demonstrated that remarkable long circulation, anti-tumor and anti-metastasis efficacy could be achieved using this drug delivery system. This work revealed a strategy for the design and preparation of anti-cancer drug delivery systems with reduced side effect, enhanced anti-tumor and anti-metastasis efficacy.
研究领域:
药学
·
肿瘤学
·
生物材料
✓ 已验证
DOI
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2024
·
IF 6.9
Weikang Guo,Wanyue Wang,Fei Lei,Ruxin Zheng,Xinyao Zhao,Yuze Gu,Mengdi Yang,Yunshun Tong,Yaoxian Wang
Cisplatin (DDP) resistance poses a significant challenge in the treatment of ovarian cancer. Studies have shown that the combination of certain polysaccharides derived from plants with DDP is an effective approach to overcoming drug resistance in some cancers. Angelica sinensis (Oliv.) Diels has been used for centuries in China to treat gynecological ailments. Numerous studies indicate that Angelica sinensis polysaccharide (ASP), an extract from Angelica sinensis , can inhibit various forms of cancer. However, the impact of ASP on ovarian cancer remains unexplored. Through both in vitro and in vivo experiments, our study revealed the capability of ASP to effectively reversing DDP resistance in cisplatin-resistant ovarian cancer cells, while exhibiting acceptable safety profiles in vivo. To elucidate the mechanism underlying drug resistance reversal, we employed RNA-seq analysis and identified GPX4 as a key gene. Considering the role of GPX4 in ferroptosis, we conducted additional research to explore the effects of combining ASP with DDP on SKOV3/DDP cells. In summary, our findings demonstrate that the combination of ASP and DDP effectively suppresses GPX4 expression in SKOV3/DDP cells, thereby reversing their resistance to DDP.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
植物科学
✓ 已验证
DOI
PubMed
高影响因子
APOPTOSIS
·
2025
·
IF 8.1
Miao Jintian,Jiang Xinyan,Wang Siyun
Cisplatin resistance significantly hinders the efficacy of ovarian cancer treatment, presenting a major challenge in improving patient outcomes. This study identifies the m6A reader protein YTHDF1 as a key regulator of cisplatin resistance in ovarian cancer through its modulation of the FZD7/Wnt/β-catenin signaling pathway. Using cisplatin-resistant ovarian cancer cell lines (A2780/DDP and SKOV3/DDP), we observed elevated YTHDF1 expression, which positively correlated with tumor cell proliferation and migration. Silencing YTHDF1 reduced FZD7 expression, inhibited Wnt/β-catenin signaling, and restored cisplatin sensitivity both in vitro and in vivo. Mechanistic investigations revealed that YTHDF1 binds to m6A-modified FZD7 mRNA, enhancing its stability and translation. Functional studies in xenograft mouse models demonstrated that targeting YTHDF1 suppressed tumor growth and enhanced apoptosis in cisplatin-resistant ovarian cancer cells. These findings highlight the YTHDF1-FZD7 axis as a novel therapeutic target for overcoming cisplatin resistance, paving the way for improved treatment strategies in ovarian cancer.
研究领域:
肿瘤学
·
分子生物学
·
表观遗传学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Biomaterials and Tissue Engineering
·
2018
·Vol. 8
·期 3
·426-432
·
IF 0.781
Hu Jinghui,Wang Li,Shen Heping,Huang Yujie,Zhao Wei
The elevated expression of mammalian target of rapamycin (mTOR) is associated with the occurrence, progression, and drug resistance of various tumors. Studies have shown overexpression of mTOR and reduced expression of miR-101 in cervical cancer tissues. Bioinformatic analysis has revealed
that a targeting binding site exists between miR-101 and the 3'-UTR of mTOR mRNA. In this study we determined whether miR-101 played a role in regulating mTOR expression and influencing the proliferation, apoptosis, and drug resistance to cisplatin (DDP) of CC cells. The regulatory relationship
between miR-101 and mTOR was validated by dual-luciferase reporter gene assay. The DDP resistance cell line, CaSki/DDP, was established, and the expressions of miR-101, mTOR, p-mTOR, and p-4EBP1 in the CaSki/DDP cell line and parental CaSki cells. The effect of DDP treatment on the proliferation
and apoptosis of the two cell lines were detected by flow cytometry. CaSki/DDP cells were divided into the following four transfection groups: miR-NC group; miR-101 mimic group; si-NC group; and si-mTOR group. The expression of miR-101, MTOR, p-mTOR, and p-4EBP1 was determined, and the effect
of DDP treatment on the proliferation and apoptosis of the two cell lines we detected by flow cytometry. There was a targeted regulatory relationship between miR-101 and mTOR. The expression and apoptosis rate of miR-101 in CaSki/DDP cells were significantly lower than CaSki cells, while the
expression and proliferation of mTOR, p-mTOR, and p-4EBP1 in CaSki/DDP cells were significantly higher than CaSki cells. The transfection of miR-101 mimic or si-mTOR significantly reduced the expression of mTOR, p-mTOR, and p-4EBP1 in CaSki/DDP cells and weakened the cell proliferation ability.
DDP treatment significantly increased the apoptosis rate. The decreased expression of miR-101 is associated with CaSki/DD cell resistance to DDP. Overexpression of miR-101 can reduce the resistance of cervical cancer CaSki/DDP cells to DDP by targeted inhibition of the expression of mTOR.
研究领域:
肿瘤学
·
分子生物学
·
癌症研究
✓ 已验证
DOI
高影响因子
MATERIALS RESEARCH BULLETIN
·
2012
·
IF 2.105
Jing Liu,Lu Wang,Jing Wang,Lantong Zhang
A new solvothermal method is proposed for the preparation of Fe 3 O 4 nanoparticles (NPs) from iron acetylacetonate in the presence of oleylamine and n- hexane. The products are characterized by X-ray powder diffraction, infrared (IR) spectroscopy, transmission electron microscopy, thermogravimetry/differential thermogravimetry (TG/DTG) analysis, and vibrating sample magnetometery. The new procedure yields superparamagnetic monodispersed Fe 3 O 4 particles with sizes ranging from 7 nm to 12 nm. The nanocrystal sizes are controlled by adjusting the volume ratio of oleylamine to n- hexane. IR and TG/DTG analyses indicate that the oleylamine molecules, as stabilizers, are adsorbed on the surface of Fe 3 O 4 NPs as bilayer adsorption models. The surface adsorption quantities of oleylamine on 7.5 and 10.4 nm-diameter Fe 3 O 4 NPs are 18% and 11%, respectively. The hydrophobic surface of the obtained nanocrystals is passivated by adsorbed organic solvent molecules. These molecules provide stability against agglomeration, enable solubility in nonpolar solvents, and allow the formation of magnetic polymer micelles.
研究领域:
材料科学
·
纳米技术
·
化学工程
✓ 已验证
产品关联
DOI
高影响因子
CHINESE JOURNAL OF POLYMER SCIENCE
·
2014
·Vol. 32
·期 10
·1329-1337
·
IF 1.42
Zhang Yan,Wang Xiao-ju,Guo Miao,Yan Hu-sheng,Wang Chen-hong,Liu Ke-liang
Multifunctional nanocarriers with multilayer core-shell architecture were prepared by coating superparamagnetic Fe 3 O 4 nanoparticles with diblock copolymer folate-poly(ethylene glycol)- b -poly(glycerol monomethacrylate) (FA-PEG- b -PGMA), and triblock copolymer methoxy poly(ethylene glycol)- b -poly(2-(dimethylamino) ethyl methacrylate)- b -poly(glycerol monomethacrylate) (MPEG- b -PDMA- b -PGMA). The PGMA segment was attached to the surfaces of Fe 3 O 4 nanoparticles, and the outer PEG shell imparted biocompatibility. In addition, folate was conjugated onto the surfaces of the nanocarriers. Cisplatin was then loaded into the nanocarrier by coordination between the Pt atom in cisplatin and the amine groups in the inner shell of the multilayer architecture. The loaded cisplatin showed pH-responsive release: slower release at pH 7.4 ( i.e. mimicking the blood environment) and faster release at more acidic pH ( i.e. mimicking endosome/lysosome conditions). All of the cisplatin-loaded nanoparticles showed concentration-dependent cytotoxicity in HeLa cells. However, the folate-conjugated cisplatin-loaded carriers exhibited higher cytotoxicity in HeLa cells than non-folate conjugated cisplatin-loaded carriers.
研究领域:
药学
·
纳米医学
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2018
·
IF 3.457
Guowen Wang,Zuyi Wang,Chuankui Li,Guixin Duan,Kangwu Wang,Qicai Li,Tao Tao
One approach to improve the targeted therapeutic efficiency of lung cancer is to deliver drugs using nano-scaled systems. In this study, RGD peptide-modified, paclitaxel (PTX) prodrug-based, dual-drugs loaded, and redox-sensitive lipid-polymer nanoparticles were developed and the in vitro and in vivo antitumor efficiency was evaluated in lung cancer cells and tumor bearing animal models. RGD-modified PTX and cisplatin (CDDP) loaded LPNs (RGD-ss-PTX/CDDP LPNs) have sizes around 190 nm, and zeta potentials of −35 mV. The half-maximal inhibitory concentration (IC50) values were 26.7 and 75.3 μg/mL for drugs loaded LPNs and free drugs combination, which indicates significantly higher antitumor activity of LPNs than free drugs. RGD-ss-PTX/CDDP LPNs also exhibited the best antitumor efficiency in vivo , which inhibited the tumor size of mice from 1486 mm 3 to 263 mm 3 . The results illustrated that the system could successfully load drugs and achieve synergistic combination lung cancer treatment efficiency with lower systemic toxicity compared with free drugs counterparts. The resulting system could be facilitated as a promising targeted nanomedicine for the treatment of lung cancer.
研究领域:
药学
·
肿瘤学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBON
·
2015
·
IF 6.196
Zhan Zhou,Qianming Wang,Jinyong Wang,Cheng Cheng Zhang
New chemical sensors based on lanthanide emission that enable sequential detection of two targets in live cells have been developed. The indicator molecules (unsaturated europium complexes) were covalently immobilized on carbon quantum dots (CQDs), and a water soluble fluorescent nano-probe ( CQDs-DTPA-Eu ) with biocompatibility was fabricated. A novel stepwise assembly method was used to generate unique responses to two different targets sequentially. Rapid and highly selective detection of tetracycline (Tc) in water and milk (detection limit 32 nM) were demonstrated. The in situ generated CQDs-DTPA-EuTc was non-emissive, but, upon addition of hydrogen peroxide (detection limit 21 nM) intense red luminescence was observed. Highly reproducible results were obtained in Plat-E cells, demonstrating the identification of tetracycline and H 2 O 2 in cellular environment with high accuracy.
研究领域:
生物化学
·
分析化学
·
细胞生物学
✓ 已验证
产品关联
DOI
高影响因子
DYES AND PIGMENTS
·
2017
·
IF 3.473
Yanhua Lai,Ping Zhao,Zhan Zhang,Bai Li,Junchen Wu
The self-assembled peptide cargo carrier with the ability of probe offered an effective strategy to deliver and track the anticancer drug, cisplatin (DDP) in ovarian cancer cells. This simple peptide system containing a pyrene fluorogen and arginine-glycine-aspartic acid (RGD) sequence could be utilized to release DDP in situ by the specific recognition between an RGD motif and α v β 3 integrin that was over-expressed on ovarian cancer cells. Importantly, we found that the disassembly-triggered peptide nanofibers , PA1, could effectively combine with DDP and release DDP in the cytoplasm with the pyrene fluorescence restoring. Moreover, the peptide cargo carrier efficiently penetrated tumour cells for enhancing therapeutic efficacy. Our system could open the door for the delivery of anticancer drug in cancer-related therapy.
研究领域:
生物化学
·
肿瘤学
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2017
·Vol. 5
·期 48
·9546-9557
·
IF 4.543
Shao-Lu Li,Yaoyi Wang,Jingfang Zhang,Wei Wei,Hua Lu
We describe here a novel targeting polyion complex (Tg-PIC) system for the delivery and intracellular release of cisplatin. Briefly, a guanidinium-pendant Pt(IV)-backboned poly-prodrug termed P(DSP-Gu) is prepared with excellent aqueous solubility, high drug-loading and high potency. To enable prolonged circulation and selective cellular internalization, P(DSP-Gu) is complexed with anisamide-end-capped poly(ethylene glycol)-block-poly(L-phosphotyrosine)-block-poly(L-leucine) (AA-PEG-PpY-PLeu) to yield Tg-PIC via electrostatic coacervation. Tg-PIC is stabilized by hydrogen bonding between phosphate and guanidinium, the PEG corona, and the helical poly(L-leucine) segment forming the hydrophobic core. The anisamide group, a high affinity ligand recognizing the sigma (σ) receptors that are overexpressed on many human malignancies including prostate cancer, is incorporated at the surface of the Tg-PIC for active targeting and efficient internalization. In vitro, the Tg-PICs show targeted and efficient internalization into sigma receptor-positive PC3 cells, and can release toxic Pt(II) species due to the degradation of P(DSP-Gu) under the intracellular reducing conditions. In vivo, the Tg-PICs exhibit superior antitumor efficacy with reduced toxicity. Thus, the system holds considerable promise towards more effective and safe nanomedicine.
研究领域:
肿瘤学
·
药剂学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2021
·
IF 9.381
Guanghui Hou,Junmin Qian,Min Guo,Weijun Xu,Jinlei Wang,Yaping Wang,Aili Suo
It is still a huge challenge for concurrent highly efficient loading of chemotherapeutic agent and photosensitizer into single nanocarrier via stimuli-responsive linkages due to their different physicochemical properties and pharmacokinetics . Herein, based on the discovery of unique cisplatin-hydrazide and cisplatin-indocyanine green (ICG) coordination reactions, a multifunctional coordination nanoprodrug, cisplatin/ICG co-loaded hydrazided hyaluronan/bovine serum albumin (HBCI) nanoparticles , was developed by a desolvation-dual coordination process. The nanoprodrug exhibited ultrahigh drug loading efficiency and glutathione/NIR light dual-responsive drug release behavior. In vitro cellular studies demonstrated efficient internalization and apoptosis-inducing ability of the nanoprodrug in HepG2 cells. In vivo results confirmed the efficacious tumor accumulation and biosafety of HBCI nanoprodrug and synergistic effect of HBCI-based combined photodynamic chemotherapy on inhibiting tumor growth. Overall, this work not only provides a novel dual coordination approach for highly efficient loading of cisplatin and ICG but also verifies the therapeutic potential of HBCI nanoprodrug in combating hepatocellular carcinoma.
研究领域:
药学
·
肿瘤学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
·
2022
·Vol. 100
·期 7
·
IF 2.245
Yanzhen Han,Yan Zhou,Liyuan Zhou,Xiaoyan Jia,Xiangjun Yu,Xiaohong An,Zhe Shi
Chemotherapy is one of the most important strategies in the treatment of cancer; however, chemoresistance restricts the effect of chemotherapy. Growing reports suggest that chloride channel-3 (ClC-3) is involved in regulating the sensitivity of multiple chemotherapeutic agents in the chemotherapy of various tumours, while its role in the chemotherapy of cholangiocarcinoma (CCA) is still poorly understood. Herein, we observed that ClC-3 was highly expressed in CCA chemoresistant tissues and CCA cisplatin-resistant cells QBC939/DDP, and the sensitivities of QBC939 and QBC939/DDP cells to cisplatin were all increased after inhibition of ClC-3. Further mechanism exploration revealed that ClC-3 knockdown reduced the level of autophagy. Furthermore, in both QBC939 and QBC939/DDP cells, the autophagy agonist rapamycin eliminated the increased cisplatin sensitivity of ClC-3 knockdown without affecting ClC-3 expression. Collectively, all the findings demonstrate that ClC-3 knockdown increases cisplatin-induced cell death in CCA cells though inhibiting autophagy, regardless of the occurrence of cisplatin resistance. In addition, our results also suggest that targeted inhibition of ClC-3 may be a potential strategy for chemosensitization in CCA chemotherapy.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）