ACS Applied Materials & Interfaces
·
2019
·
IF 8.456
Xiaoting Liu,Xiaowen Xu,Yi Zhou,Nan Zhang,Wei Jiang
Overexpression of adenosine 5′-triphosphate-binding cassette transporters is one of the primary causes of drug resistance in cancer. Downregulating the expression of these transporters by inhibiting the mRNA translation process is an effective approach to cope up with this situation. Herein, multifunctional molecular beacons (MBs)-modified gold nanoparticle (AuNP) as a nanocarrier (MBs-AuNP) is developed for synergistic inhibition and in situ imaging of drug-resistant-related mRNAs in living cells. MBs-AuNP is composed of (i) triple specially designed molecular beacons modified on the surface of AuNP, for binding drug-resistant-related mRNAs, loading doxorubicin (Dox), and reporting the fluorescence signal, and (ii) AuNP, for loading MBs, introducing them into cells, and quenching their fluorescence. After uptake by cells, MBs-AuNP will hybridize with three different drug-resistant-related mRNAs (MDR1 mRNA, MRP1 mRNA, and BCRP mRNA), respectively, which could inhibit their translation to decrease efflux protein expression and lead to AuNP-quenched fluorescence recovery for in situ imaging. Real-time quantitative-polymerase chain reaction and western blot results showed that drug-resistant-related mRNAs and efflux proteins expression both decreased. Dox-loaded MBs-AuNP exhibited higher suppression efficacy compared to that of free Dox against HepG2/ADR (0.35 vs 1.06 μM of IC50) and MCF-7/ADR (2.78 vs >5 μM of IC50). Direct observation of intracellular hybridization events and differentiation of drug-resistant cancer cells or non-drug-resistant cancer cells could be accomplished through fluorescence imaging analysis. This nanocarrier is capable of downregulating the expression of multiple efflux proteins by gene silencing, allows in situ monitoring of silencing events, and thus provides a powerful strategy to cope up with drug resistance at the gene level.
研究领域:
纳米技术
·
癌症生物学
·
分子生物学
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药学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
EUROPEAN POLYMER JOURNAL
·
2018
·
IF 3.741
Yu Zhang,Pan He,Xinming Liu,Hongyu Zhang,Huailin Yang,Chunsheng Xiao,Xuesi Chen
Synthetic polymers that can change their physicochemical properties in response to physiological stimuli have attracted particular interest for constructing smart drug delivery systems. In the present work, a novel oxidation-responsive block copolymer bearing thioether pendants was designed and synthesized by ring-opening alternating copolymerization (ROAP) of phthalic anhydride (PA) and 2-(methylthio)ethyl glycidyl ether (MTG) monomer using mPEG-OH as the macroinitiator and a phosphazene base, t -BuP 1 , as the catalyst. The obtained mPEG- b -P(PA- alt -MTG) copolymer could self-assemble into spherical micelles in water with an average size of about 30 nm and a critical micelle concentration value of 7.44 × 10 −3 mg/mL. 1 H NMR results indicated that the hydrophobic thioether group can be selectively oxidized to hydrophilic sulfoxide by H 2 O 2 , leading to disassociation of the micelles as illustrated by the TEM observation. Nile Red, as a model drug, was loaded into the copolymer micelles. The intensity of the fluorescence emission decreased sharply after addition of H 2 O 2 , indicating an oxidation-triggered drug release. Moreover, the drug-loaded micelles could be effectively internalized into MCF-7 cells, as indicated by the confocal laser scanning microscopy (CLSM) and flow cytometry (FCM) studies. MTT assay further demonstrated that the synthesized copolymer showed good biocompatibility towards L929 cell, even at a concentration up to 0.5 mg/mL. In sum, this kind of copolymer may have great potential applications in oxidation responsive drug delivery.
研究领域:
材料科学
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药学
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聚合物化学
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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
高影响因子
STEROIDS
·
2014
·
IF 2.716
Bin Yu,Ping-Ping Qi,Xiao-Jing Shi,Li-Hong Shan,De-Quan Yu,Hong-Min Liu
A series of novel steroidal pyran–oxindole hybrids were efficiently synthesized in a single operation through the vinylogous aldol reaction of vinyl malononitrile 3 with substituted isatins involving the construction of C–C and C–O bonds. Some compounds displayed moderate to good cytotoxicity against T24, SMMC-7721, MCF-7 and MGC-803 cells. Compounds 4f and 4i were more potent than 5-Fu against T24 and MGC-803 cells with the IC 50 values of 4.43 and 8.45 μM, respectively. Further mechanism studies indicated that compound 4i induced G2/M arrest and early apoptosis in a concentration- and time-dependent manner.
研究领域:
药物化学
·
肿瘤学
·
合成化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
APPLIED SURFACE SCIENCE
·
2014
·
IF 2.538
Juan Wu,Yujiao Wang,Wei Jiang,Shanshan Xu,Renbing Tian
This study focuses on the synthesis and characterization of recyclable clusters of magnetic nanoparticles (CMNPs) as doxorubicin carriers for cancer therapy. Fe 3 O 4 nanoparticles were used as magnetically responsive carriers, the modified polyethylene glycol dicarboxylic acid (APS-PEG-TFEE) acted as a steady bridge between Fe 3 O 4 and drug. The prepared CMNPs exhibited a size within 20 nm, good stability and super-paramagnetic responsibility ( M s 62.02 emu/g); doxorubicin (DOX) can be successfully loaded to CMNPs at a loading rate of 76.19% by electrostatic interaction. Moreover, the release studies in vitro showed that the drug-loaded carriers (CMNPs-DOX) had excellent pH-sensitivity, 76.16% of DOX was released within 72 h at pH 4.0, and the secondary drug loading rate was nearly 52%. WST-1 assays in model breast cancer cells (MCF-7) demonstrated that CMNPs-DOX exhibited high anti-tumor activity, while the CMNPs were practically non-toxic. Thus, our results revealed that CMNPs would be a competitive candidate for drug delivery carriers and CMNPs-DOX could be used in targeted cancer therapy in the near future.
研究领域:
纳米技术
·
药学
·
癌症研究
·
材料科学
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产品关联
DOI
高影响因子
CHEMICAL RESEARCH IN CHINESE UNIVERSITIES
·
2018
·Vol. 34
·期 2
·229-234
·
IF 1.248
Yu Yang,Ma Wei,Yu Lina,Zhou Shuyuan,Zhu Guangshan,Shi Wei
In this paper, antibody-modified silica nanoparticles were successfully synthesized, and their average di-ameter was (109±9) nm. These particles were mixed with cell extracts to target a protein, then, an antibody labeled with fluorescein isothiocyanate(FITC) was added to form FITC-labeled nanoparticle complexes and the product was analyzed using flow cytometry. The results confirm that the intracellular proteins and biomarkers were precisely and sensitivity detected by the novel method in vitro . The FITC intensity of Akt antibody-conjugated particles was in-creased ≥10-fold compared with that of control samples in MCF-7 cells. Furthermore, it can also simultaneously measure several proteins when modified with different antibodies.
研究领域:
纳米技术
·
生物化学
·
细胞计量学
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蛋白质组学
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癌症研究
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2017
·
IF 3.649
Bolin Cheng,Binbin Lu,Xuan Liu,Tingting Meng,Yanan Tan,Yun Zhu,Na Liu,Hong Yuan,Xuan Huang,Fuqiang Hu
Though Drug delivery systems have achieved accumulation at tumor sites via passive targeting and active targeting, the therapeutic effects are far from perfect. The unsatisfactory results are mainly due to limited drug release from the nanocarriers at tumor sites, while the pharmacological activities of the drug are attributed to the concentration of the free drug and the time maintained at the pharmacological targets. A pH-responsive chitosan based glycolipid-like nanocarrier (CSO-FBA-SA) was fabricated by conjugating stearyl alcohol (SA) to chitosan oligosaccharide (CSO) with the linkage of 4-formylbenzoic acid (FBA). FBA was a kind of aromatic aldehyde carbonyl compounds, which can form the benzoic-imine bond. In the presence of a Schiff’s base structure, the carrier showed improved properties and could be quickly degraded in an acidic environment. In order to explore the process and mechanism of the nanocarriers in focal cells, the method for determining the intracellular concentration of released free doxorubicin was established, and the time-dependent change of the DOX-loaded micelles was revealed. The sight of drug release was also obtained with CLSM. The cytotoxicity of the CSO-FBA-SA/DOX against human breast cancer MCF-7 cells increased by 2.75-fold and 3.77-fold in comparison with the CSO-SA/DOX and DOX, respectively. Furthermore, the CSO-FBA-SA/DOX showed a 2.12-fold higher cytotoxicity against the MCF-7 cells than that treated against human ovarian cancer SKOV-3 cells with lower intracellular pH value, which indicated that the cellular inhibition positively correlated with the intracellular pH value. High tumor accumulation and fast drug release of the CSO-FBA-SA/DOX in tumor was responsible for the remarkable tumor growth inhibitory effect. Moreover, the CSO-FBA-SA/DOX could selectively respond to the acidic environment and release DOX in tumor only, which had relatively minimal cytotoxicity towards normal tissues. The results showed that this newly developed glycolipid-like nanocarrier could act as a potential vector for delivering the drug effectively with a low systemic toxicity.
研究领域:
药学
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纳米技术
·
癌症研究
·
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
Acta Biomaterialia
·
2017
·
IF 6.319
Yanan Kang,Lu Lu,Jinshuai Lan,Yue Ding,Jing Yang,Yong Zhang,Yuan Zhao,Tong Zhang,Rodney J.Y. Ho
A novel redox-sensitive system for co-delivering hydrophobic drugs and hydrophilic siRNA or shRNA was developed by conjugating gambogic acid (GA) with poly(amido amine)s (PAAs) through amide bonds, which is called GA-conjugated PAAs (PAG). PAG can self-assemble into micelles as amphiphilic block copolymers , which exhibits an excellent loading ability for the co-delivery of docetaxel (DTX) and MMP-9 shRNA with adjustable dosing ratios. In addition, confocal microscopy , flow cytometry and in vitro transfection analyses demonstrated more efficient cellular internalization of DTX and MMP-9 shRNA after incubation with PAG/DTX- MMP-9 shRNA micelles (PAG/DTX-shRNA) than with free drugs. Unlike traditional amphiphilic copolymer micelles, GA conjugated in PAG possesses an intrinsic anticancer efficacy. The presence of disulfide bonds in PAAs enables rapid disassembly of PAG micelles in response to reducing agents, inducing the release of loaded drugs (DTX, GA and MMP-9 shRNA). In vitro cellular assays revealed that PAG/DTX-shRNA micelles inhibited MCF-7 cell proliferation more efficiently than the single drug or single drug-loaded micelles. In vivo biodistribution and anti-tumor effect studies using an MCF-7 breast cancer xenograft mouse model have indicated that PAG/DTX-shRNA micelles can enhance drug accumulation compared with the free drug, thereby sustaining the therapeutic effect on tumors. Additionally, PAG/DTX-shRNA micelles displayed a greater anti-tumor efficacy than Taxotere® and PAG-shRNA micelles. These results suggest that the redox-sensitive PAG platform is a promising co-delivery system for combining drugs and gene therapy for the treatment of cancer. Statement of Significance The PAG micelles were designed by conjugating gambogic acid (GA) with poly(amido amine)s (PAAs), which would serve dual purposes as both gene and drugs co-delivery carrier and an anti-tumor prodrug. Unlike traditional amphiphilic micelles, GA conjugated in PAG could exert its intrinsic efficacy and provide synergistic antiproliferative effects with docetaxel (DTX) on MCF-7 cells. Disulfide bonds in PAG enables a rapid disassembly of PAG micelles in response to reducing agents and to release all loaded drugs (DTX, GA and MMP-9 shRNA) at tumor sites. PAG/DTX-shRNA micelles displayed greater anti-tumor efficacy than that of Taxotere®, indicating the design concept for PAG works well. And the strategy for PAG could be used to develop a series of similar co-delivery systems through conjugations of other small-molecule drugs with PAAs, such as doxorubicin , methotrexate and other drugs with carboxy groups in their structure.
研究领域:
药学
·
纳米技术
·
癌症研究
·
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
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS
·
2016
·Vol. 105
·期 5
·1114-1125
·
IF 2.881
Shu-Di Yang,Wen-Jing Zhu,Qiao-Ling Zhu,Wei-Liang Chen,Zhao-Xiang Ren,Fang Li,Zhi-Qiang Yuan,Ji-Zhao Li,Yang Liu,Xiao-Feng Zhou,Chun Liu,Xue-Nong Zhang
The development of effective and stable carriers of small interfering RNA (siRNA) is important for treating cancer with multidrug resistance (MDR). We developed a new gene and drug co-delivery system and checked its characteristics. Low-density lipoprotein (LDL) was coupled with N-succinyl chitosan (NSC) Lipoic acid (LA) micelles and co-delivered MDR1 siRNA and paclitaxel (PTX-siRNA/LDL-NSC-LA) to enhance antitumor effects by silencing the MDR gene of tumors (Li et al., Adv Mater 2014;26:8217-8224). In our study, we developed a new type of containing paclitaxel-loaded micelles and siRNA-loaded LDL nanoparticle. This “binary polymer” is pH and reduction dual-sensitive core-crosslinked micelles. PTX-siRNA/LDL-NSC-LA had an average particle size of (171.6 ± 6.42) nm, entrapment efficiency of (93.92 ± 1.06) %, and drug-loading amount of (12.35% ± 0.87) %. In vitro, MCF-7 cells, high expressed LDL receptor, were more sensitive to this delivery system than to taxol ® and cell activity was inhibited significantly. Fluorescence microscopy showed that PTX-siRNA/LDL-NSC-LA was uptaken very conveniently and played a key role in antitumor activity. PTX-siRNA/LDL-NSC-LA protected the siRNA from degradation by macrophage phagocytosis and evidently down-regulated the level of mdr1 mRNA as well as the expression of P-gp. We tested the target ability of PTX-siRNA/LDL-NSC-LA in vivo in tumor-bearing nude mice. Results showed that this system could directly deliver siRNA and PTX to cancer cells. Thus, new co-delivering siRNA and antitumor drugs should be explored for solving MDR in cancer. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1114–1125, 2017.
研究领域:
药学
·
生物医学工程
·
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
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2022
·
IF 6.51
Hongyan Zhang,Jiandong Yu,Lisha Ma,Yue Zhao,Shujun Xu,Jingbin Shi,Ke Qian,Mancang Gu,Hongsheng Tan,Li Xu,Yun Liu,Chaofeng Mu,Yang Xiong
Multi-drug resistance (MDR) in breast cancer poses a great threat to chemotherapy. The expression and function of the ATP binding cassette (ABC) transporter are the major cause of MDR. Herein, a linear polyethylene glycol (PEI) conjugated with dicyandiamide, which called polymeric metformin (PolyMet), was successfully synthesized as a simple and biocompatible polymer of metformin. PolyMet showed the potential to reverse MDR by inhibiting the efflux of the substrate of ATP-binding cassette (ABC) transporter from DOX resistant MCF-7 cells (MCF-7/DOX). To test its MDR reversing effect, PolyMet was combined with DOX to treat mice carrying MCF-7/DOX xenografts. In order to decrease the toxicities of DOX and delivery PolyMet and DOX to tumor at the same time, PolyMet was complexed with poly-γ-glutamic acid-doxorubicin (PGA-DOX) electrostatically at the optimal ratio of 2:3, which were further coated with lipid membrane to form lipid/PolyMet-(PGA-DOX) nanoparticles (LPPD). The particle size of LPPD was 165.8 nm, and the zeta potential was +36.5 mV. LPPD exhibited favorable cytotoxicity and cellular uptake in MCF-7/DOX. Meanwhile, the bioluminescence imaging and immunohistochemical analysis indicated that LPPD effectively conquered DOX-associated MDR by blocking ABC transporters (ABCB1 and ABCC1) via PolyMet. Remarkably, LPPD significantly inhibited the tumor growth and lowered the systemic toxicity in a murine MCF-7/DOX tumor model. This is the first time to reveal that PolyMet can enhance the anti-tumor efficacy of DOX by dampening ABC transporters and activating the AMPK/mTOR pathway, which is a promising strategy for drug-resistant breast cancer therapy.
研究领域:
肿瘤学
·
药理学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2022
·
IF 6.14
Xinyue Wei,Ziyin Xiang,Weili Xue,Shengfu Chen
Although nanodelivery has made unprecedented progress in enhancing the efficacy of chemotherapeutic drugs, there is still much room for improvement. Zwitterionic nanodrugs have great potential to be a universal platform for nanodelivery because of the exceptional hemocompatibility and ultralow immunogenicity, although they are sensitive to the tumor microenvironment (TME) for tumor cell targeting and internalization. Here, a negatively biased zwitterionic peptide micelle, a mimic of albumin, was developed to improve two vital factors, which are the responsive transition of stability and affinity to tumor cells from circulation to the slightly acidic TME. The incorporation of positively charged hydrophobic phenformin into the camptothecin (CPT)-conjugated micelles (Pep-SSetc-CPT@Phen) can make the micelles more compact to reduce premature drug release in circulation while improving the sensitivity of the micelles to MCF-7-xenografted tumors by tuning their zeta potential in the TME. Thus, Pep-SSetc-CPT@Phen exhibited more tumor-preferred biodistribution and longer blood circulation than nonphenformin-incorporated micelles (Pep-SSetc-CPT), thereby enhancing tumor growth inhibition with lower side effects. Together, these results have provided a promising combinational method to enhance the transition of stability and the sensitivity to the TME for developing biomimetic zwitterionic nanodrugs with high antitumor efficacy.
研究领域:
纳米技术
·
药学
·
肿瘤学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
Biomaterials Advances
·
2023
·
IF 0
Le Wang,Jianye Yang,Xueyan Hu,Shuping Wang,Yanxia Wang,Tongyi Sun,Dan Wang,Wenchi Wang,Hailin Ma,Yingshuai Wang,Kedong Song,Wenfang Li
Distal metastasis of breast cancer is a primary cause of death, and the lung is a common metastatic target of breast cancer. However, the role of the lung niche in promoting breast cancer progression is not well understood. Engineered three-dimensional (3D) in vitro models capable of bridging this knowledge gap can be specifically designed to mimic crucial characteristics of the lung niche in a more physiologically relevant context than conventional two-dimensional systems. In this study, two 3D culture systems were developed to mimic the late stage of breast cancer progression at a lung metastatic site. These 3D models were created based on a novel decellularized lung extracellular matrix/chondroitin sulfate/gelatin/chitosan composite material and on a porcine decellularized lung matrix (PDLM), with the former tailored with comparable properties (stiffness, pore size, biochemical composition, and microstructure) to that of the in vivo lung matrix. The different microstructure and stiffness of the two types of scaffolds yielded diverse presentations of MCF-7 cells in terms of cell distribution, cell morphology, and migration. Cells showed better extensions with apparent pseudopods and more homogeneous and reduced migration activity on the composite scaffold compared to those on the PDLM scaffold. Furthermore, alveolar-like structures with superior porous connectivity in the composite scaffold remarkably promoted aggressive cell proliferation and viability. In conclusion, a novel lung matrix-mimetic 3D in vitro breast cancer lung metastasis model was developed to clarify the underlying correlativity between lung ECM and breast cancer cells after lung colonization. A better understanding of the effects of biochemical and biophysical environments of the lung matrix on cell behaviors can help elucidate the potential mechanisms of breast cancer progression and further improve target discovery of therapeutic strategies.
研究领域:
癌症生物学
·
组织工程
·
生物医学工程
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
JOURNAL OF MATERIALS SCIENCE
·
2023
·Vol. 58
·期 21
·8952-8968
·
IF 4.5
Qi Wenxia,Wang Shenglan,Yang Heng,Luo Tingting,Zhao Feng,Han Jingtian,Zhang Jing
Combination chemotherapy is a crucial therapeutic strategy to improve the therapeutic efficacy of breast cancer in clinic. When combined with photodynamic therapy (PDT), the therapeutic efficacy can be further enhanced not only by PDT-induced phototoxicity, but also by PDT-induced photochemical internalization which facilitates the intracellular delivery and endo/lysosomes escape of drugs, therefore exhibit considerable potential in clinical treatment of breast cancer. Herein, a novel cocktail therapeutic strategy based on albumin-based nanosystem was established by covalently modifying human serum albumin (HSA) with all-trans retinoic acid (RA) and chlorin e6 (Ce6) to form HSA-RA-Ce6 (HRC) conjugate, and using paclitaxel (PTX) to induce self-assembly of HRC to form HRC@PTX nanoparticles (HRC@PTX NPs). The HRC@PTX NPs could amplify the therapeutic efficacy of combination chemotherapy of RA and PTX with Ce6-mediated PDT. The HRC@PTX NPs were characterized with a mean particle size of 174.1 ± 2.1 nm and a slightly negative zeta potential and exhibited good stability and hemocompatibility. The HRC@PTX NPs could promote the cellular uptake of drugs by MCF-7 cells and MDA-MB-231 cells and produce ROS to amplify the synergistic anti-tumor efficacy. The in vitro inhibitory effects on tumor growth investigated on monolayer and three-dimensional tumor spheroids revealed that HRC@PTX NPs exhibited significantly higher anti-tumor activity when exposed to 660-nm laser. These results demonstrated that HRC@PTX NPs could be developed as a promising cocktail therapeutic strategy for synergistic breast cancer therapy. Graphical abstract
研究领域:
肿瘤学
·
药学
·
纳米技术
·
癌症治疗
✓ 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）