Journal of Nanomaterials
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2022
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IF 3.791
Shujuan Ouyang,Youqun Tang,Yanming Cao
Lymphoma is one of the most common malignancies of blood system, and drug resistance is an important cause of treatment failure. Multidrug resistance gene P-glycoprotein (P-gp) plays an important role in lymphoma chemotherapeutic drug resistance. Our previous studies have found that P-gp is highly expressed in doxorubicin-resistant lymphoma cells (Daudi/R). With the development of nanotechnology, a large number of nanomaterials have been applied in various biomedical fields. Therefore, in this study, P-gp inhibitor tariquidar (TAR) and chemotherapy drug doxorubicin were loaded onto gold nanoshells (AuNSs) to construct TAR-AuNSs/Dox nanodrug system. TAR and Dox were slowly released from TAR-AuNSs/Dox in an acidic tumor microenvironment. TAR-AuNSs/Dox increased the uptake of Dox by drug-resistant lymphoma cells and inhibited P-gp expression to reduce Dox pumping. Compared to the free Dox, TAR-AuNSs/Dox had a stronger killing effect on Daudi/R cells, which provided a new therapeutic strategy for the treatment of drug-resistant lymphoma.
研究领域:
纳米技术
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肿瘤学
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药学
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生物医学工程
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产品关联
DOI
高影响因子
IET Nanobiotechnology
·
2022
·Vol. 17
·期 2
·49-60
·
IF 2.05
Liu-Jing Wen,Yue-Sheng Wang,Jie Zhang
The aim of this study was to provide a new effective carrier for rescuing the sensitivity of drug-resistant in breast cancer cells. Nano-gold micelles loaded with Dox and Elacridar (FP-ssD@A-E) were chemically synthesised. With the increase in the amount of Dox and Elacridar, the encapsulation rate of FP-ssD@A-E gradually increased, and the drug loading rate gradually decreased. FP-ss@A-E had a sustained-release effect. Dox, Elacridar, FP-ss@AuNPs, and FP-ssD@A-E significantly improved cell apoptosis, in which, FP-ssD@A-E was the most significant. FP-ssD@A-E significantly decreased the cell viability and improved the Dox uptake. The levels of VEGFR-1, P-gp, IL-6, and i-NOS were significantly decreased after Dox, Dox + Elacridar, FP-ss@AuNPs, and FP-ssD@A-E treatment. It was worth noting that FP-ssD@A-E had the most significant effects. The prepared FP-ssD@A-E micelles, which were spherical in shape, uniform in particle size distribution, and had good drug loading performance and encapsulation efficiency.
研究领域:
药学
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肿瘤学
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纳米技术
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
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2020
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IF 2.69
Qianqian Qi,Xianwu Zeng,Licong Peng,Hailiang Zhang,Miao Zhou,Jingping Fu,Jianchao Yuan
Herein, we construct a charge - switchable polymer nano micelles poly (2-(hexamethyl eneimino) ethyl methacrylate) - b - poly (ethylene glycol) monomethyl ether methacrylate) - b - poly (diethyl enetriaminepentaacetic acid methacrylate) - b - poly (1-vinyl imidazole) - b - poly (4-vinyl phenylboronic acid) (PC7A-PEG-DTPA-VI-PBA) in different pH solutions. DOX released faster from micelles in a weakly acidic environment (pH 5.0) than at pH 7.4. In order to enhance the anti-tumor effect, the imidazole functional groups in the polymer were used to coordinate CdSeTe quantum dots (QDs) for photodynamic treatment (PDT). In addition, the surfaces of the micelles were further decorated with phenylboronic acidas a targeting group, using DTPA chelating 99mTc for SPECT imaging.It has been successfully demonstrated that the nanoparticles have a good cumulative effect on the tumor site.The structure of the polymer was characterized by 1HNMR. The morphology and particle size of the micelles were characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The drug loading capacity (DLC) and drug loading efficiency (DLE) of the micelles were analyzed by ultraviolet visible spectroscopy. And the pH-sensitive drug release and cytotoxicity of the micelles were verified in vitro. In vitro experiments showed that the nano micelles were noncytotoxic to different cell lines, while DOX@CdSeTe@PC7A-PEG-DTPA-VI-PBA inhibited the proliferation and promoted the apoptosis of B16F10 cells. An in vivo study with C57BL tumor-bearing mice indicated that DOX@CdSeTe@PC7A-PEG-DTPA-VI-PBA nano micelles efficiently inhibited tumor growth. Results showed that the nano micelles had good pH responsibility and biocompatibility, and the loaded DOX could be released in the weak acidic environment of tumor cells, and it was expected to be a good drug delivery system.
研究领域:
药剂学
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生物医学工程
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
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2013
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IF 2.404
Chao Du,Jun Shi,Jin Shi,Li Zhang,Shaokui Cao
Hybrid CaCO 3 microparticles coated by sodium poly(styrene sulfonate) (PSS) and aliphatic poly(urethane-amine) (PUA) were developed as thermal-/pH-responsive drug delivery vehicles via LbL self-assembly technique. The DOX release from the CaCO 3 microparticles was higher than 60% within 36 h, whereas the value of PUA/PSS-coated microparticles was only 20%. The results demonstrated that the PUA/PSS multilayer coating could reduce the drug release rate and significantly assuage the initial burst release of DOX. In addition, the drug release of the hybrid microparticles was found to be thermal-/pH-dual responsive. More interestingly, more than 90% of DOX was released in 36 h at pH 2.1 and 55 °C owing to the combined action of the dissolution of the CaCO 3 core and the shrinkage of aliphatic PUA.
研究领域:
药剂学
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生物材料学
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2016
·Vol. 5
·期 19
·2517-2527
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IF 5.76
Xiaoman Mao,Jingxing Si,Qian Huang,Xuanrong Sun,Qianzhi Zhang,Youqing Shen,Jianbin Tang,Xiangrui Liu,Meihua Sui
Doxorubicin (DOX) is a widely used chemotherapeutic drug to treat a range of cancers. However, its unfavorable effects, particularly the cardiotoxicity and the induction of multidrug resistance (MDR), significantly limit its clinical applications. Herein, a novel doxorubicin prodrug, PEG 2K -DOX, is synthesized by conjugating a deprotonated doxorubicin molecule with the polyethylene glycol (PEG, MW: 2K) chain via pH-responsive hydrazone bond, and its potential as a better alternative than doxorubicin is evaluated. The data show that the amphiphilic PEG 2K -DOX can self-assemble into stable nanoparticles with a high and fixed doxorubicin loading content (≈20 wt%), a favorable size of 91.5 nm with a narrow polydispersity (PDI = 0.14), good stability, and pH-dependent release behavior due to the acid-cleavable linkage between PEG and doxorubicin. Although doxorubicin hardly accumulates in MDR cells, PEG 2K -DOX nanoparticles significantly increase the cellular uptake and cell-killing activity of doxorubicin in two MDR cancer cell lines MCF-7/ADR and KBv200, with the IC 50 values dropped to 1.130% and 42.467% of doxorubicin, respectively. More impressively, PEG 2K -DOX nanoparticles exhibit significantly improved plasma pharmacokinetics, increased in vivo therapeutic efficacy against MDR xenograft tumors, and better in vivo safety compared with doxorubicin. PEG 2K -DOX nanoparticles hold the promise to become a better alternative than doxorubicin for cancer treatment, especially for MDR tumors.
研究领域:
药学
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肿瘤学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
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2022
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IF 5.589
Chuanjiang Jian,Ying Wang,Huijun Liu,Zongning Yin
Although synergistic effects of photothermal therapy (PTT) and chemotherapy for cancer have been extensively investigated in previous studies, more potential strategies need to be exploited to alleviate severe adverse effects. In this study, a biotin-modified and activatable nanotheranostic system is developed. This system (BPSP/DOX-CyBA) composed of H 2 O 2 -sensitive thioketal (TK) linker, hydrophilic biotin-decorated polyethylene glycol (PEG) segment, hydrophobic polycaprolactone (PCL) segment, could self-assemble into (99 ± 1.3) nm nanoparticles and co-deliver H 2 O 2 -triggered photosensitizer CyBA and cytotoxic drugs DOX to tumor site. In vitro , DOX and CyBA could release rapidly from nanoparticles, CyBA accumulation in the mitochondria causes mitochondrial damage, leading to mitochondrial dysfunctions,while rising the level of ROS in B16F10 cells, and further to promote the micells to trigger release. CyBA could be activated into CyOH and the photothermal therapy was turn “off” into “on”. In BPSP/DOX-CyBA group, the local temperature within tumor reached 50 °C and cell apoptosis rate reached 68.6% under Laser irradiation (650 nm, 1 W/cm 2 ). Fluorescence microscopy and flow cytometry analysis further demonstrated the better uptake efficiency on B16F10 cells with biotin decoration. In a mice B16F10 tumor model, the group with co-delivery CyBA and DOX had the best tumor retention effect, the maximal local temperature increasement and the minimum tumor growth with negligible side effects, suggesting the potential of BPSP/DOX-CyBA nanopalteform that synergistic photothermal therapy and chemotherapy and mitochondria damage as an effective melanoma treatment strategy.
研究领域:
肿瘤学
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药剂学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2023
·
IF 5.9
Jiaojiao Chen,Yarong Song,Wenqian Yang,Jianhui Guo,Saihui Zhang,Dong Wan,Yonghui Liu,Jie Pan
Chemotherapy remains the primary treatment for cancer; however, conventional chemotherapeutic drugs have several shortcomings, including poor solubility, lack of targeting, low bioavailability, and high toxicity to healthy tissues. In order to overcome these limitations, drug delivery systems (DDS) have emerged as a promising alternative. In this study, we synthesized TPGS3350-PVGLIG-SS-DOX polymeric micelles that incorporate both extracellular MMP2/9 enzyme response and intracellular reduction response at a nanoscale level. The micelles remained stable throughout the blood circulation and only aggregated at the tumor sites, thanks to the enhanced permeability and retention (EPR) effect. Moreover, the tumor tissue showed a high expression of MMP2/9 enzymes, which resulted in the cleavage of the PVGLIG peptide sequence, ultimately leading to an improved phagocytosis efficiency. Under the action of high intracellular GSH concentration, the disulfide bond was broken and DOX was released to induce tumor cell death. The TPSD&D micelles exhibited good tumor inhibitory activity in vivo and significantly reduced toxic side effects on normal tissues. Our work provides a simple method to assemble tumor-targeted prodrug micelles to improve cancer therapy, which holds potential for clinical applications in antitumor therapy.
研究领域:
药剂学
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肿瘤学
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生物材料学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Zhiyuan Niu,Shengbo Wu,He Ding,Xuexia Shan,Yuting Shen,Yuanbo Peng,Junjie Song,Shaoyue Li,Weichen Xu,Ying Wang,Mingliang Pei,Xiaodong Hou
Currently, while intravenous chemotherapy effectively targets tumor lesions, it also causes unavoidable systemic toxicity due to drug metabolism in the bloodstream and the toxicity to normal cells. To address this problem, an injectable and biodegradable fibrin-based gel was employed as a pharmacy scaffold, cladding FDA-approved DOX-loaded and hyaluronic acid (HA)-modified nanoparticles (DOX&FeP-HA@gel), aiming to achieve local tumor therapy through the combination of ferroptosis-DOX mediated self-enhancement therapy. The DOX&FeP-HA exhibited remarkable CD44 bio-targeting, medium stability, TME-triggered degradation, and continued release of drugs, achieving approximately 80 % cumulative release within 48 h. During this process, the released DOX induced apoptosis and generated abundant H 2 O 2 by mitochondrial activity. Simultaneously, intracellular H 2 O 2 reacted with Fe 2+ to produce highly toxic OH. Moreover, DOX&FeP-HA not only consumed GSH but also reduced GPX4 expression in tumor cells, thereby amplifying ferroptosis. To anchor nanoparticles in tumor tissue, an injection that utilizes fibrin-based gel was introduced. In live experiments, 4T1 tumor-bearing mice received optimal therapeutic outcomes with DOX&FeP-HA@gel treatment, achieving a 100 % survival rate over 30 days according to Kaplan-Meier survival analysis. Overall, a strategy of in situ injection gel carrying multifunctional nanoparticles was proposed, offering a promising new approach to tumor treatment with substantial potential for clinical applications.
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Tianyuan Xu,Lu Fan,Li Wang,Haozhen Ren,Qingfei Zhang,Weijian Sun
Drug delivery systems based on hydrogel microcarriers have shown enormous achievements in tumor treatment. Current research direction mainly concentrated on the improvement of the structure and function of the microcarriers to effectively deliver drugs for enhanced cancer treatment with decreased general toxicity. Herein, we put forward novel hierarchical mesoporous silicon nanoparticles (MSNs) and bovine serum albumin (BSA) composite microparticles (MP MSNs@DOX/FU ) delivering doxorubicin (DOX) and 5-fluorouracil (FU) for effective tumor therapy with good safety. The DOX and FU could be efficiently loaded in the MSNs, which were further encapsulated into methacrylate BSA (BSAMA) microparticles by applying a microfluidic technique. When transported to the tumor area, DOX and FU will be persistently released from the MP MSNs@DOX/FU and kept locally to lessen general toxicity. Based on these advantages, MP MSNs@DOX/FU could observably kill liver cancer cells in vitro, and evidently suppress the tumor development of liver cancer nude mice model in vivo. These results suggest that such hierarchical hydrogel microparticles are perfect candidates for liver cancer treatment, holding promising expectations for impactful cancer therapy.
研究领域:
药剂学
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肿瘤学
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生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG TARGETING
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2021
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IF 5.121
Kun Ma,Wenzhe Li,Guang Zhu,Hao Chi,Yalin Yin,Yijing Li,Yan Zong,Zhaoming Guo,Li Wang,Weiping Xu,Changhao Cui,Huiwei Zhou,Jianqiang Xu
Nano graphene oxide (NGO) has high drug-loading capacity due to its huge surface area. However, the limited stability and the poor biocompatibility of NGO hampered its application as drug delivery carrier under physiological conditions. Thereby, a new strategy of using chemical conjugation on NGO with hydrophilic polymers was adopted but currently was too complicated, low yield and costly. In this study, doxorubicin-hyd-PEG-folic acid (DOX-hyd-PEG-FA) polymers were coated on the surface of NGO via π–π stocking and the hydrophobic effect between DOX and NGO. With the PEG shell protection, the biocompatibility of NGO was significantly improved. The drug-loading capacity of nanoparticles was more than 100%. FA ligands on the nanoparticle could guide the nanoparticles actively targeting to tumour cells. The hydrazone bond between DOX and PEG was decomposed spontaneously in the weakly acidic environment, which made PEG layer dissociated from NGO. Furthermore, DOX was easily protonized at low pH conditions, which weakened the interaction between DOX and NGO. Thus, DOX could be released rapidly from the nanoparticles in tumour cells. In summary, NGO@DOX-hyd-PEG-FA is an easy-prepared nanoparticle with excellent biocompatibility, high pH-sensitivity and active tumour targeting. Therefore, it is a promising multifunctional nanocarrier effective for targeted drug delivery.
研究领域:
生物医学工程
·
药剂学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2017
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IF 6.319
Rongrong Zhu,Zhaoqi Wang,Peng Liang,Xiaolie He,Xizhen Zhuang,Ruiqi Huang,Mei Wang,Qigang Wang,Yechang Qian,Shilong Wang
Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis and is highly expressed in carcinoma, which make it an important target for tumor targeting therapy. Neuroblastoma is the main cause for cancer-related death in children. Like most solid tumors, it is also accompanied with the overexpression of VEGF. Doxorubicin Hydrochloride (DOX), a typical chemotherapeutic agent, exhibits efficient anticancer activities for various cancers. However, DOX, without targeting ability, usually causes severe damage to normal tissues. To overcome the shortages, we designed a novel nano-composite, which is Bevacizumab (Bev) modified SiO 2 @LDH nanoparticles (SiO 2 @LDH-Bev), loading with DOX to achieve targeting ability and curative efficiency. SiO 2 @LDH-DOX and SiO 2 @LDH-Bev-DOX nanoparticles were synthesized and the physicochemical properties were characterized by TEM detection, Zeta potential analysis, FTIR, Raman and XPS analysis. Then in vitro and in vivo anti-neuroblastoma efficiency, targeting ability and mechanisms of anti-carcinoma and anti-angiogenesis of SiO 2 @LDH-Bev-DOX were explored. Our results indicated that we obtained the core-shell structure SiO 2 @LDH-Bev with an average diameter of 253 ± 10 nm and the amount of conjugated Bev was 4.59 ± 0.38 μg/mg SiO 2 @LDH-Bev. SiO 2 @LDH-Bev-DOX could improve the cellular uptake and the targeting effect of DOX to brain and tumor, enhance the anti-neuroblastoma and anti-angiogenesis efficiency both in vitro and in vivo, and alleviate side effects of DOX sharply, especially hepatic injury. In addition, we also demonstrated that angiogenesis inhibitory effect was mediated by DOX and VEGF triggered signal pathways, including PI3K/Akt, Raf/MEK/ERK, and adhesion related pathways. In summary, SiO 2 @LDH-Bev could be a potential VEGF targeting nanocarrier applied in VEGF positive cancer therapy. Statement of Significance This paper explored that a novel core-shell structure nanomaterial SiO 2 @LDH and modified SiO 2 @LDH with Bevacizumab (Bev) to form a new tumor vasculature targeting nanocarrier SiO 2 @LDH-Bev as vector of DOX, which was not reported before. The results indicated that SiO 2 @LDH-Bev could improve the VEGF targeting ability, anti-neuroblastoma and anti-angiogenesis efficiency of DOX. At the same time, SiO 2 @LDH-Bev-DOX could erase the cardiac toxicity and hepatic injury coming from DOX. Tube formation showed SiO 2 @LDH-Bev-DOX had the strongest effect on inhibiting angiogenesis among all the four formulations. SiO 2 @LDH-Bev-DOX could downregulate expression of p-VEGFR and inhibit activation of the Raf/MEK/ERK, p38MAPK, PI3K/Akt and FAK signaling pathways to achieve the goal of anti-angiogenesis. This work provides a novel system for the safe and efficient use of Bev and DOX on Neuroblastoma and explores the mechanism of the function of nano carrier in cancer therapy both in vitro and in vivo.
研究领域:
癌症生物学
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药学
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纳米技术
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分子生物学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2016
·
IF 3.42
Yaming Gu,Yizhen Guo,Changyong Wang,Jiake Xu,Jianping Wu,Thomas Brett Kirk,Dong Ma,Wei Xue
It is a promising way to treat the multi drug resistance (MDR) of tumor cells in both of drug and gene methods. A polyamidoamne dendrimer functionalized graphene oxide (GO-PAMAM) was designed, which could load doxorubicin (DOX) and MMP-9 shRNA plasmid at the same time in order to achieve effective treatment to breast cancer. GO-PAMAM has a high loading capacity to DOX and pH-controlled DOX release. Besides, it has efficient gene transfer ability, the transfection efficiency is significantly better than PEI-25k in the presence of serum, and it can significantly inhibit the expression of MMP-9 protein in MCF-7 cells. The effect of DOX and MMP-9 shRNA plasmid co-delivery was more significant than that of the single drug. Moreover, GO-PAMAM exhibited lower cytotoxicity compared to PEI-25k in CCK-8 assays, and also showed a good biocompatibility in vivo . Therefore, GO-PAMAM will have broad prospects for drug and gene co-delivery.
研究领域:
生物医学工程
·
肿瘤学
·
纳米医学
✓ 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）