INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2024
·
IF 5.3
Liqiao Zhang,Xinyu Cao,Jiayi Chen,Yanyan Dong,Wenwen Chen,Yu Gao,Jingjing Guo,Haiqin Huang
Multidrug resistance (MDR) poses a significant impediment to the efficacy of chemotherapy in clinical settings. Despite Paclitaxel (PTX) being designated as the primary pharmaceutical agent for treating recurrent and metastatic breast cancer, the emergence of PTX resistance frequently results in therapeutic shortcomings, representing a substantial obstacle in clinical breast cancer management. In response, we developed a delivery system exhibiting dual specificity for both tumors and mitochondria. This system facilitated the sequential administration of small interfering B-cell lymphoma-2 (siBcl-2) and PTX to the tumor cytoplasm and mitochondria, respectively, with the aim of surmounting PTX resistance in tumor cells through the activation of the mitochondrial apoptosis pathway. Notably, we employed genetic engineering techniques to fabricate a recombinant ferritin containing the H-subunit (HFn), known for its tumor-targeting capabilities, for loading siBcl-2. This HFn-siBcl-2 complex was then combined with positively charged Triphenylphosphine-Liposome@PTX (TL@PTX) nanoparticles (NPs) to formulate HFn/siBcl-2@TL/PTX. Guided by HFn, these nanoparticles efficiently entered cells and released siBcl-2 through the action of triphenylphosphine (TPP)-mediated “proton sponge,” thereby precisely modulating the expression of Bcl-2 protein. Simultaneously, PTX was directed to the mitochondria through the accurate targeting of TL@PTX, synergistically initiating the mitochondrial apoptosis pathway and effectively suppressing PTX resistance both in vitro and in vivo . In conclusion, the development of this dual-targeting delivery system presents a promising therapeutic strategy for overcoming PTX resistance in the clinical treatment of breast cancer.
研究领域:
肿瘤学
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药学
·
分子生物学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF POLYMER SCIENCE
·
2025
·
IF 3.6
Sunqi Yu,Siyuan Chen,Tianrui Tong,Yunfeng Yan,Qi Shuai
Micelle-based drug delivery systems (DDS) have emerged as a promising solution to address challenges associated with the in vivo delivery of hydrophobic anticancer chemotherapeutics. However, micelles still encounter issues such as drug pre-leakage and poor stability in physiological conditions. To overcome these limitations, we developed a core-cross-linking strategy utilizing amphiphilic copolymers, mPEG- b- P(AVL- co -LA) (mPPAL), functionalized with phenylboronic acid (PBA), and catechol by CuAAc “click” chemistry, respectively. These copolymers self-assembled into core-cross-linked micelles (CLMs), featuring boronic ester bonds, which were characterized through a series of evaluations. The CLMs exhibited a rational particle size, uniform morphology, low critical micelle concentration (CMC), high PTX loading capacity, and excellent stability. Two promising micelles, CLM1 and CLM3, were identified, and their responsiveness to acidic pH and elevated levels of ROS was confirmed to enable controlled PTX release. The results of MTT assay and hemolytic analysis demonstrated high biocompatibility and potential in vivo application of these selected CLMs. The anticancer efficacy of the selected PTX-CLMs was further validated through MTT assay and 3D tumor spheroid studies. Fluorescence microscopy and flow cytometry demonstrated rapid intracellular uptake of the CLMs. In vivo biodistribution studies demonstrated successful accumulation in the targeted tumor tissue. These findings suggest that the boronic ester-based CLMs developed in this study are a promising nanocarrier for effective PTX delivery. Graphical Phenylboronic acid (PBA) and catechol-modified amphiphilic copolymers (mPPAL@R) were synthesized via ring-opening polymerization followed by CuAAc click chemistry. These copolymers were employed to construct pH- and ROS-dual-responsive micelles with boronic ester core-crosslinking. A series of in vitro and in vivo experiments were conducted to evaluate PTX-loaded micelles, demonstrating their significant potential for effective PTX delivery.
研究领域:
药剂学
·
肿瘤学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
Nano Research
·
2020
·Vol. 13
·期 1
·273-281
·
IF 8.183
Zhang Tao,Jiang Zhenqi,Chen Libin,Pan Chunshu,Sun Shan,Liu Chuang,Li Zihou,Ren Wenzhi,Wu Aiguo,Huang Pintong
As nanomedicine-based clinical strategies have continued to develop, the possibility of combining chemotherapy and singlet oxygen-dependent photodynamic therapy (PDT) to treat pancreatic cancer (PaC) has emerged as a viable therapeutic modality. The efficacy of such an approach, however, is likely to be constrained by the mechanisms of drug release and tumor oxygen levels. In the present study, we developed an Fe(III)-complexed porous coordination network (PCN) which we then used to encapsulate PTX (PCN-Fe(III)-PTX) nanoparticles (NPs) in order to treat PaC via a combination of chemotherapy and PDT. The resultant NPs were able to release drug in response to both laser irradiation and pH changes to promote drug accumulation within tumors. Furthermore, through a Fe(III)-based Fenton-like reaction these NPs were able to convert H 2 O 2 in the tumor site to O 2 , thereby regulating local hypoxic conditions and enhancing the efficacy of PDT approaches. Also these NPs were suitable for use as a T 1 -MRI weighted contrast agent, making them viable for monitoring therapeutic efficacy upon treatment. Our results in both cell line and animal models of PaC suggest that these NPs represent an ideal agent for mediating effective MRI-guided chemotherapy-PDT, giving them great promise for the clinical treatment of PaC.
研究领域:
肿瘤学
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放射学
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纳米医学
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治疗诊断学
✓ 已验证
产品关联
DOI
高影响因子
MACROMOLECULAR BIOSCIENCE
·
2015
·Vol. 15
·期 10
·1411-1422
·
IF 3.851
Yan-Ling Luo,Mei Han,Feng Xu,Ya-Shao Chen,Yong-Qin Zhang
pH-Responsive H-type poly(methylacrylic acid- block -four hydroxyl terminated poly(butadiene-acrylobitrile)- block -poly(methylacrylic acid (PMAA 2 - b -HTPBN- b -PMAA 2 ) block copolymers were synthesized via atom transfer radical polymerization and the follow-up hydrolysis, and characterized by 1 H NMR, FT-IR and SEC . The block copolymers could self-assemble into nanoscale spherical core-shell micelle aggregates in aqueous solution, and the physicochemical properties depended on the system composition and pH media, with pH phase transition at 5.7–6.1. The copolymer micelle aggregates exhibited pH-triggered drug release and cytotoxicity, and could potentially be used as drug targeting release carriers.
研究领域:
材料科学
·
药学
·
生物医学工程
✓ 已验证
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2016
·
IF 3.994
Dujuan Zhao,Huiyuan Zhang,Shengfeng Yang,Wenxiu He,Yuxia Luan
The main cause of multidrug resistance (MDR) is overexpression of active efflux transporters, such as P-glycoprotein (P-gp). To reverse MDR and improve the chemotherapy effect of paclitaxel (PTX), we propose a new drug delivery system based on mixed micelles constructed with d -α-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS) and the mPEG-SS-PTX conjugate with consideration that TPGS is a P-gp inhibitor that can block the cancer cell action of pumping drugs outside of cells and can enhance the anticancer effect. mPEG-SS-PTX is synthesized by conjugating hydrophilic mPEG with a hydrophobic drug, PTX, via a redox-sensitive disulfide bond. The mPEG-SS-PTX conjugate is amphiphilic and can self-assemble in water. Mixed micelles formed by the mPEG-SS-PTX conjugate and TPGS have a low critical micelle concentration (CMC, ∼1.05 × 10 −3 mg/mL) and high drug loading content (∼19.6%). The disulfide bond in the mPEG-SS-PTX conjugate can be broken in cancer cells (a reductive environment) and release PTX to kill cancer cells. In vitro cytotoxicity and cell uptake suggest that mixed micelles can effectively improve the accumulation of PTX in multidrug-resistant MCF-7 cells. Therefore, the present as-prepared mixed micelles very effectively reverse the MDR and enhance the therapeutic effect.
研究领域:
药学
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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
Nanoscale
·
2024
·
IF 5.8
yaoyao guo,Manzhen Li,xinxin liu,xi wang,ziqi zhang,dongchun liu,Xiangtao Wang
Nearly all the anti-tumor drugs can benefit greatly from tumor-targeted delivery for improved therapeutic efficacy and reduced toxic side effects. However, the vast majority of tumor-targeting ligands can only target to specific tumor cells highly expressed the corresponding receptors and thus applicable to limited tumor types. Heptadecyanines with medium cyclohexene and medium -Cl atoms, such as IR780 and IR808, have shown an unusual ability to indiscriminately accumulate into virtually all tumor types. In this study, IR808 was conjugated with DSPE-mPEG2000-NH2 and the resultant DSPE-PEG2000-IR808 (DP-IR808) in combination with TPGS, successfully encapsulated paclitaxel (PTX) and immunomodulator R848 into nanoparticles with a small particle size of 150.20 nm, a negative charge of -16.50 mV, rod-like morphology and a PTX loading content of 31.6 %. The obtained DP-IR808@PTX-R848 NPs rapidly accumulated into 4T1 tumors with a tumor/liver fluorescence ratio of 1.71 and a significant photothermal effect and could be directly used for NIR imaging. DP-IR808@PTX-R848 NPs achieved a high tumor inhibition rate of 94%, a mean survival time of > 90 d and a tumor-free survival percentage of 57%. As far as we know, this was the first time that nanoparticles were modified with heptamethylcyanine molecules. Nanoparticles based on DSPE-PEG-IR808, which integrates tumor targeted drug delivery, in vivo infrared imaging and photothermal therapy, is expected to become a versatile drug delivery platform for tumor therapy.
研究领域:
药剂学
·
肿瘤学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2019
·
IF 4.471
Weiguang Li,Jianpeng Xue,Hanmei Xu
Background S-HM-3 is a tumor angiogenesis inhibitor with short half-life (25 min). In this present, TPGS/Solutol polymeric micelles was prepared to load together insoluble paclitaxel (PTX) and soluble S-HM-3, expecting to together deliver them to the tumor site with long-circulating, targeting function and combating multi-drug resistance (MDR). Materials and methods PTX and S-HM-3 loaded TPGS/Solutol micelles (PHTSm) were prepared by the method of thin-film evaporation, and characterized by dynamic light scattering, transmission electron microscope (TEM), atomic force microscopy (AFM) and releasing properties. The anticancer effect of the polymeric micelles system was evaluated and confirmed by experiments of in vitro cell uptake study, in vivo pharmacokinetics, and pharmacodynamics studies. Results Micelles exhibited smooth spherical morphology with 20~30 nm and low critical micelle concentration (CMC) value of 0.000124 mg/mL. Only about 30% of PTX were slowly released from micelles at 48h, which can beneficial to the long circulation in blood. The results of in vitro cell assay proved that S-HM-3 could be easier to get into MDA-MB-231 cell, and its angiogenesis inhibition ability was also enhanced after integrating into micelles. In particular, the results of in vivo studies showed that the half-life of S-HM-3 and PTX was significantly prolonged 25.27 and 5.54 folds, and their AUC 0–∞ was enhanced 129.78 and 15.65 times, respectively. Meanwhile 83.05% tumor inhibition rate of PHTSm was achieved compared with 59.99% of PTX. Conclusions TPGS and Solutol micelles hold promising potential to resolve the conundrum of combined therapy of cytotoxic drug and angiogenesis inhibitor with different physicochemical property and anticancer mechanism in clinical use.
研究领域:
药学
·
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
BIOMATERIALS
·
2017
·
IF 8.402
Zhu Jin,Keqin Wu,Jingwen Hou,Kunhong Yu,Yuanyuan Shen,Shengrong Guo
An antitumor drug/esophagus stent combination can palliatively relieve malignant esophageal stricture and exert local chemotherapy to cancer. It is vital for effective treatment of cancer to control drug release and facilitate drug penetration into deep tissue after the combination is placed in the malignant strictured esophagus part. In this study, we firstly designed and prepared a novel antitumor drug/esophagus stent combination: a magnetocaloric nitinol stent coated with a bilayered film that consisted of one ethylene-vinyl acetate copolymer (EVA) layer as drug blocking layer and one EVA layer containing 10% paclitaxel (PTX) and 30% temperature sensitive phase-change fatty alcohol (1-tetradecanol, 1-hexadecanol or 1-octadecanol). The drug release and penetration into rabbit esophagus wall from the combination were investigated. It was found that, under an alternating electromagnetic field at a power of 0.1 kW, the combination was heated to 43 °C, the PTX was faster and more released from the combination, as well as the amount of PTX in esophagus tissue or its deep muscle tissue penetrated from the combination was much higher than that without alternating electromagnetic field. The pathological data showed that the combination was biocompatible and safe after placement in rabbit esophagus even under an alternating electromagnetic field. Overall, the PTX could be magnetocalorically released and effectively penetrated into esophagus wall from the PTX/nitinol stent combination.
研究领域:
生物医学工程
·
肿瘤学
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
APPLIED SURFACE SCIENCE
·
2025
·
IF 6.9
Yuan Ma,Nanpu Cheng,Chunhong Li,Muhammad Aizaz Ud Din,Lan Zhao,Nengcong Pan,Yuhan Lei
The development of low-platinum electrocatalysts with high activity in alkaline media is critical for sustainable and cost-effective hydrogen production. In this study, we report a dual-phase engineering strategy to synthesize Pt-CoSe 2 nanoparticles embedded in nitrogen-doped carbon (Pt-CoSe 2 @NC) via controlled pyrolysis of ZIF-67. The resulting catalyst features hierarchical porosity and a 3D conductive network that confines ultrafine Pt particles and enhances interfacial charge and mass transfer. Strong Pt-CoSe 2 interactions induce electron redistribution, elevating cobalt oxidation states and optimizing hydrogen adsorption energetics. Nitrogen doping and surface-oxygenated Co species further boost performance. The optimized Pt-CoSe 2 @NC catalyst exhibits an overpotential of 37.4 mV at 10 mA cm −2 , a Tafel slope of 60.4 mV dec -1 , and remains over 90 % of its initial current density after 24 h in 1 M KOH. Density functional theory (DFT) calculations reveal a shift in the d -band center of Pt due to Pt-CoSe 2 interface formation, leading to near-thermoneutral hydrogen adsorption energy. This work integrates MOF-derived structural control with electronic interface modulation, offering a generalizable blueprint for designing efficient, low-noble-metal HER catalysts.
研究领域:
材料科学
·
电催化
·
能量存储与转换
·
纳米材料
·
密度泛函理论
✓ 已验证
产品关联
DOI
高影响因子
DRUG DELIVERY
·
2023
·
IF 6
Xiaoyan Xu,Tianhao Zhou,Xudong Wei,Xuelian Jiang,Jiyan Cao
Although surgery-based comprehensive therapy is becoming the main approach to treat laryngeal cancer, recurrence, metastasis, radiotherapy resistance and chemotherapy tolerance are still the main causes of death in patients. Targeted inhibition of laryngeal cancer stem cells has been considered as the consensus to cure laryngeal cancer. Our previous study has confirmed proto-oncogene Bmi-1 as a key regulator for self-renewal of laryngeal cancer stem cells. Targeted knockdown of Bmi-1 gene effectively inhibited the self-renewal and differentiation of laryngeal cancer stem cells, leading to the promoted sensitivity to chemotherapy including paclitaxel. However, due to off-target effects and quick degradation of the naked Bmi-1-RNAi small RNA oligo by nuclease in body fluids, it is urgently needed to develop a tumor-targeted delivery system with a protective shell. In this study, we designed and synthesized cRGD peptide-modified chitosan-polyethylene glycol slow-release nanoparticles (mPEG-CS-cRGD/Bmi-1RNAi-PTX) containing Bmi-1RNAi siRNA oligo and paclitaxel, which showed spherical in shape, 200 nm diameter in size, low cytotoxicity, strong DNA wrapping, resistance to nuclease degradation and high transfection efficiency to cells. Functional analysis indicated significant suppression of cell proliferation and migration and induction of apoptosis by the nanocomplex in laryngeal cancer cells in vitro. By application to the mouse model with laryngeal cancer, the nanocomplex inhibited tumor growth significantly in vivo. In addition, cRGD peptide, paclitaxel and Bmi-1 siRNA in the nanoparticles showed synergistic effects to suppress laryngeal cancer stem cells. In conclusion, this study not only developed a laryngeal tumor-targeted chemotherapeutic system, but also demonstrated a Bmi-1 RNAi-based chemotherapeutic strategy to inhibit cancer stem cells, having strong potential to treat laryngeal cancer patients suffering therapy resistance and/or tumor recurrence.
研究领域:
肿瘤学
·
纳米技术
·
分子生物学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2021
·
IF 4.384
Yuping Wei,Caiying Zhang,Man Zhang,Qionghong Niu,Fengli Hui,Zi Liu,Xia Xu
In our previous study, a novel cell penetrating peptide (CPP) R7 (Arg-Arg-Arg-Arg-Arg-Trp-Trp, RRRRRWW) has been developed to help cellular internalization of paclitaxel (PTX) through the non-covalent interaction with CPP. However, the facilitation mechanism of R7 mediated PTX translocation is not clear. Here the uptake pathways of R7 and R7-PTX were investigated by in vitro test and molecular simulations. In vitro experiments reveal that both R7 and R7-PTX complex translocate through the direct translocation and clathrin mediated endocytosis and associate with the macropinocytosis pathway at high CPP concentration. The translocation of R7(0.1 mM)-PTX complex further involves the lipid raft/caveolae mediated endocytosis. The simulation results show that the synergistic effect between R7 and PTX not only changes the penetration energy barrier but also activates the macropinocytosis and lipid raft/caveolae mediated pathway, resulting in the improvement in the translocation. The presence of heparin also improves the R7 and R7-PTX translocation. These studies provide a theoretical basis for understanding PTX delivery facilitated by the synergistic effect between CPP and cargo and paves a way for CPP design.
研究领域:
药学
·
分子生物学
·
细胞生物学
·
生物物理学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DALTON TRANSACTIONS
·
2017
·Vol. 46
·期 7
·2204-2213
·
IF 4.029
Lanfang Ren,Xijian Liu,Qian Wang,Lijuan Zhang,Guoying Deng,Feng Zhou,Jie Lu
In this study, a multifunctional nano-drug (PTX-loaded Cys-Fe3O4/CuS@BSA nanocomposite), which performs well in hydrophobic drug delivery, magnetic resonance imaging (MRI) and chemo-photothermal combination therapy, has been successfully synthesized via a facile method with several biocompatible agents. The characterization verified that our as-obtained nanocarrier has a preferable average diameter of about 300 nm for cancer therapy, shows a great MRI ability and magnetism performance, and exhibits a favorable in vitro and in vivo photothermal therapeutic efficacy by introducing CuS, and the sustained release of chemotherapeutics could be controlled by pH value and near-infrared laser irradiation has further enhanced the therapeutic performance. Overall, the excellent synergistic effect to inhibit tumor growth effectively realized via imaging-guided combinational chemo-photothermal therapy in the present work, highlights the promise of conquering the limitations of tumor treatments.
研究领域:
生物医学工程
·
癌症治疗
·
纳米技术
·
分子影像
✓ 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）