INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
·
IF 7.7
Mo Liu,Zi-xu Zhang,Jia-hua Wang,Rui-bo Guo,Lu Zhang,Liang Kong,Yang Yu,Juan Zang,Yang Liu,Xue-tao Li
Ovarian cancer, a highly lethal form of gynecological cancer globally, has witnessed notable advancements in its treatment through the integration of nanotechnology and immunotherapy. Here, we designed a novel astragalus polysaccharide vector (PDA), encapsulating podophyllotoxin (PPT), and modifying methotrexate (DSPE-PEG 2000 -MTX) on its surface for targeting ovarian cancer cells with high folate receptor expression. We prepared novel MTX-modified PPT-loaded astragalus polysaccharide micelles (MTX-PPT-micelles) by dialysis method and evaluated their characterization, stability, safety and targeting ability. EDU proliferation, apoptosis, wound healing, and macrophage polarization experiments were performed, and a mouse ectopic tumor model and a lung metastasis model were established to evaluate the antitumor effects of MTX-PPT-micelles. The prepared MTX-PPT-micelles had appropriate particle size, good stability and safety, and were able to achieve slow drug release. In vitro and in vivo experiments showed that MTX-PPT-micelles significantly enhanced tumor uptake and apoptosis, and significantly inhibited tumor proliferation, invasion and metastasis processes. In addition, MTX-PPT-micelles could improve tumor immunosuppression by shifting tumor-associated macrophages from M2 to M1 phenotype. In conclusion, this study successfully constructed a novel nano-delivery system to achieve targeted therapy for ovarian cancer by combating tumor cells with immunomodulatory effects on tumor-associated macrophages.
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ACS Applied Nano Materials
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2018
·
IF 0
Jinjin Li,Zengpei Dou,Yuhong Liu,Jianbin Luo,Jinxin Xiao
Although surfactant micelles usually exhibit superlow friction at the nanoscale due to the formation of the hydration layer, the load-bearing capacity (LBC) is limited. In this study, the friction behaviors of two different surfactant micelles (fluorinated and hydrocarbon surfactants, denoted as F-surfactant and H-surfactant) were compared, with the results showing that both can achieve superlow friction (μ = 0.001–0.002) when the self-assembled micelle layers on the two surfaces were not ruptured. Although the two different surfactant micelles have the similar friction behaviors, the LBC of superlow friction for the F-surfactant is 2.5 times larger than that for the H-surfactant. The mechanisms of the superlow friction and the reasons for different LBC were investigated using an atomic force microscopy. The superlow friction can be attributed to the formation of hydration layer on the surfactant headgroups, whereas the higher LBC for F-surfactant originates from the fatness of its carbon chain, which produces the larger hydrophobic attraction and meanwhile increases the stiffness of the micelle layer.
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INTERNATIONAL JOURNAL OF FOOD PROPERTIES
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2017
·
IF 1.427
Yue Wu,Xiaoyong Wang
This work studied the potential of self-assembled micelles of casein–dextran conjugates (CD) as a protective carrier for bioactive curcumin. CD was prepared through the Amadori rearrangement of the Maillard reaction. In casein micelles and CD micelles, the addition of curcumin can quench the intrinsic fluorescence of casein gradually. According to the double logarithm equation, the binding constants were determined as 3.9 × 104 and 1.8 × 105 M−1 for the binding of curcumin with casein micelles and CD micelles, respectively. The higher affinity of hydrophobic binding of curcumin with CD micelles was ascribed to the more hydrophobic and compact structure of casein core surrounded by the hydrophilic dextran shell, which was supported by the fluorescence spectrum and fluorescence anisotropy of curcumin. Furthermore, CD micelles were found to be superior to casein micelles for improving the stability and radical scavenging activity of curcumin.
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Journal of Materials Chemistry B
·
2017
·Vol. 6
·期 3
·458-468
·
IF 4.543
Yu Sun,Yuling Bao,Xue Jiang,Songwei Tan,Mingxing Yin,Conglian Yang,Liping Zhou,Zhiping Zhang
Physical properties, such as surface charge, of nanomedicines play a crucial role in their in vivo behaviors, which could eventually determine the tumor inhibition effect. Although drug delivery systems with positive charge are effective for cell internalization, this property is universally applicable to the lack of selectivity of both tumors and normal tissues, resulting in rapid blood clearance and undesired side effects. By employing charge-reversible strategies, the dilemma can be overcome and enhanced cellular uptake, prolonged circulation time and high biocompatibility can be realized. Here, we constructed Vitamin E-based micelles with charge-reversible property for the delivery of the antineoplastic agent paclitaxel. In the slightly acidic tumor microenvironment, the micelles converted from negative to positive charge due to the cleavage of the pH-sensitive bond, leading to enhanced cellular uptake and subsequently enhanced drug release. The micelles demonstrated improved antitumor efficiency both in vitro and in vivo and improved anti-metastasis effect in 4T1 orthotopic tumor model compared with those of clinically formulated Taxol and non-sensitive micelles. Besides, the micelles showed high biocompatibility and reduced side effects. Overall, these findings highlight that the micelles with charge-reversible property have great potential for cancer therapy in clinic.
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JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2024
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IF 4.5
Chao Shen,Jianchao Li,Cong Li,Lihong Wang,Zeyu Wang,Kexin Zhang,Zehao Li,Lianrui Cao,Lijiang Chen
The pathogenesis of cancer is highly complex, and a single anti-tumor drug is insufficient to fully suppress the tumor. Doxorubicin (DOX) is a commonly used antitumor drug; however, its severe cardiotoxicity, narrow therapeutic window, and the development of multidrug resistance (MDR) significantly limit its clinical application. To overcome the limitations of single chemotherapeutic agents and improve treatment outcomes, combination therapies involving different drugs are widely used in clinical practice. In this project, the compatibility of DOX and Curcumin (Cur), Paclitaxel (PTX) with Curcumol derivatives (CD-2e) was simulated by molecular dynamics, followed by dissipative particle dynamics (DPD) simulations to investigate the self-assembly process of drug-loaded micelles and the effect of the content of encapsulated drugs on the morphology and structure of the micelles. From these, Cur, a more compatible drug, was selected for co-delivery with DOX to the tumor site in GSH-stimulated responsive micelles to control drug release in the tumor tissue, thereby enhancing drug efficacy and reducing toxic side effects. This delivery system aimed to achieve controlled drug release within the tumor tissue, thereby enhancing drug efficacy and reducing toxic side effects. In vitro and in vivo experiments confirmed the stability and compatibility of the mPEG–SS–DOX/Cur micelles, demonstrating their potent antitumor effects and ability to mitigate drug-induced toxicity under redox conditions.
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Nature Communications
·
2025
·Vol. 16
·期 1
·1-10
·
IF 15.7
Lu Shuo,Liu Yashuang,Dong Jinfeng,Li Xuefeng
Here are described the dilution-driven gel-sol-gel-sol transitions in aromatic hydrotrope/zwitterionic surfactant bi-component aqueous mixtures. Long and entangled wormlike micelles (WLMs) of concentrated erucyl dimethyl amidopropyl betaine (EAPB) solutions sequentially transform into hexagonal liquid crystal phase (H 1 ), highly concentrated spherical micelles (HCSMs), and finally hexagonal close packed micellar phase (HCP) upon gradual introducing an aromatic hydrotrope, sodium salicylate (NaSal). The HCP then successively converts into HCSMs, WLMs, and spherical micelles (SMs) upon further dilution with water, corresponding to a gel-sol-gel-sol transition. This dilution-induced HCSMs to WLMs transition results in an interesting thickening process, which is caused by a slow kinetic process, from the agglomeration and recombination of SMs to long and rigid WLMs via the intermediately formed rodlike micelles. In this work, the sustained adjustment of the competitive self-sorting and co-assembly between hydrotropes and surfactants by dilution was identified, benefitting the creation and application of WLMs fluids with switchable viscosity.
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PHARMACEUTICAL RESEARCH
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2012
·Vol. 29
·期 12
·3512-3525
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IF 4.093
Yang Rulei,Zhang Suai,Kong Deling,Gao Xuli,Zhao Yanjun,Wang Zheng
Purpose To utilize a novel type of polymer-drug conjugate micelle to enhance the delivery of low-potency curcumin. Methods Multiple curcumin molecules were conjugated to poly(lactic acid) (PLA) via tris(hydroxymethyl)aminomethane (Tris) linker producing the hydrophobic drug-binding block; methoxy-poly(ethylene glycol) (mPEG) was employed as the hydrophilic block. Micelles were characterized by size, loading capacity, stability, and critical micelle concentration (CMC). Human hepatocellular carcinoma (HepG2) cells were employed to assess cytotoxicity and intracellular targeting ability of micelles. Results mPEG-PLA-Tris-Cur micelles were within nanorange (<100 nm). CMC of such micelles (2.3 ± 0.4 μg/mL) was 10 times lower than mPEG-PLA micelles (27.4 ± 0.8 μg/mL). Curcumin loading in mPEG-PLA-Tris-Cur micelles reached 18.5 ± 1.3% (w/w), compared to traditional mPEG-PLA micelles at 3.6 ± 0.4% (w/w). IC 50 of mPEG-PLA-Tris-Cur micelles (~22 μg/mL at curcumin-equivalent dose) was similar to unmodified curcumin. Placebo and drug-encapsulated conjugate micelles could be efficiently internalized to cytoplasmic compartment of HepG2 cells. Conclusions Micelle-forming polymer-drug conjugates containing multiple drug molecules were an efficient means to increase loading and intracellular delivery of low-potency curcumin.
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Polymer Chemistry
·
2012
·Vol. 3
·期 8
·2217-2227
·
IF 5.321
Hang Lu,Lang Fan,Qiuming Liu,Jingren Wei,Tianbin Ren,Jianzhong Du
It is well known that silver nanoparticles have excellent antibacterial activities. However, to prepare well-defined, water-dispersible and long-term stable silver nanoparticles still remains insufficient. Presented in this paper are the design and preparation of new water-dispersible silver-decorated polymer vesicles and micelles based on a new kind of amphiphilic block-statistical copolymer, PEO-b-P(DMA-stat-tBA) (polymer 1) and its partially hydrolyzed derivative, PEO-b-P(DMA-stat-tBA-stat-AA) (polymer 2). Here PEO stands for poly(ethylene oxide), DMA for 2-(dimethylamino)ethyl methacrylate, tBA for t-butyl acrylate and AA for acrylic acid. PEO and poly(tBA) are designed to provide permanent hydrophilicity and hydrophobicity for macromolecular self-assembly in water, respectively. Poly(DMA) is introduced for the coordination of Ag+ ions to form silver nanoparticles in situ upon reduction. Poly(AA) is designed to serve the scaffold for the silver nanoparticle formation in the micelle core by electrostatic interactions with Ag+ ions. The silver-decorated polymer vesicles and micelles have been prepared in five steps: Firstly, polymer 1 was synthesized by Atom Transfer Radical Polymerization (ATRP) in the presence of CuBr/PMDETA in methanol at 60 °C. Secondly, a fraction of hydrophobic poly(tBA) in polymer 1 was hydrolyzed into hydrophilic and functional poly(acrylic acid) (PAA) to form polymer 2 in the presence of trifluoroacetic acid (TFA). Thirdly, polymer 1 was self-assembled into polymer vesicles with tuneable sizes ranged from 100–700 nm in basic water–DMF and polymer micelles with ∼50 nm diameter in neutral water–DMF, respectively. Polymer 2 was self-assembled into small micelles with ∼20 nm diameter by direct dissolution in water. Fourthly, the silver precursor AgNO3 was introduced into the polymer micelle or polymer vesicle solution where the Ag+ ion was absorbed in the core of the micelles or the membrane of the vesicles. Finally, the Ag nanoparticles were formed in the core of the micelles or the membrane of the vesicles when the reducing agent sodium borohydride was introduced. 1H NMR, GPC, DLS, UV and TEM were employed to characterize the structure and composition of the block copolymers, polymer micelles and vesicles, and silver-decorated polymer micelles and vesicles. Those water-dispersible silver-decorated polymer micelles and vesicles showed excellent antibacterial efficacy against Escherichia coli (E. coli) with quite low minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC).
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CARBOHYDRATE POLYMERS
·
2011
·
IF 3.463
Hongyan Zhu,Fei Liu,Jing Guo,Jianpeng Xue,Zhiyu Qian,Yueqing Gu
Folate modified chitosan micelles were synthesized for cancer-specific targeting and drug delivery. Receptor-mediated uptake and drug delivery were characterized in vitro and in a small animal model of cancer after loading with hydrophobic fluorescent dyes as drug models. Hydrophilic succinic anhydride and hydrophobic octaldehyde were reacted with chitosan respectively to form amphipathic N-succinyl-N′-octyl chitosan (SO-chitosan). SO-chitosan was covalently modified with folate to form folate-modified N-succinyl-N′-octyl chitosan (folate-SO-chitosan). The folate-SO-chitosan micelles were obtained through self-assembling and maintained a stable core-shell structure with average diameter of about 136 nm up to 15 days. The prepared folate-SO-chitosan micelles displayed a good drug loading content (12.17%), entrapment efficiency (69.32%) and sustained release behavior for the model drug fluorescein. The in vitro cellular uptake and in vivo tumor targeting ability of the folate-SO-chitosan micelles were evaluated by fluorescence microscopy and near infrared imaging, respectively. In vitro and in vivo results demonstrated enhanced targeting behaviors in a folate receptor positive tumor model (Bel-7402), which suggests that the folate-SO-chitosan micelles are promising tumor targeting carriers for hydrophobic diagnostic agents as well as anti-tumor agents.
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ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Shuo Xu,Shaorong Yan,Jun You,Xiaochen Wu
Antibacterial hydrogels have emerged as a promising approach for effective wound treatment. However, despite extensive research on the fabrication of antibacterial hydrogels, it remains challenging to develop injectable, biocompatible, transparent, and mass-producible hydrogels with antibacterial properties. In this study, we successfully fabricated an antibacterial drug-loaded composite hydrogel, named CC45/OKG40/HS, through a Schiff base reaction between carboxymethyl chitosan (CC) and oxidized konjac glucomannan (OKG), followed by the encapsulation of stevioside-stabilized honokiol (HS) micelles. The CC45/OKG40/HS hydrogel exhibited several favorable properties, including a short gel time (<10 min), high water content (>92%), injectability, good adhesiveness, self-healing ability, and high transparency. In vitro experiments confirmed its excellent antibacterial properties, antioxidant activities, and high biocompatibility (no cytotoxicity, hemolysis ratio <5%). Furthermore, in vivo evaluation demonstrated that the CC45/OKG40/HS0.5 hydrogel accelerated wound healing by relieving inflammatory responses and enhancing re-epithelization. Given its feasibility for mass production, the findings showed that the CC45/OKG40/HS hydrogel has the potential as an advanced antibacterial wound dressing for commercial use.
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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2011
·
IF 2.13
Jun Li,Mingwei Zhao,Liqiang Zheng
The wormlike micelles formed by surface active N -alkyl- N -methylpyrrolidinium bromide ionic liquids (ILs) have been investigated in aqueous solution. The typical rheological parameters and the viscoelastic properties of wormlike micelles were characterized by rheological measurements and cryogenic-transmission electron microscopy (cryo-TEM). The typical rheological parameters were further evaluated by Maxwell model and the viscoelastic properties were discussed based on the living polymer model. Cryo-TEM images confirmed the formation of wormlike micelles in aqueous solution. The effect of the hydrocarbon chain length of the ILs on the wormlike micelles formation was also studied.
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JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY
·
2017
·Vol. 17
·期 5
·2873-2880
·
IF 1.483
Huang Saiyan,Liu Jieying,Zhu Hao,Hussain Abid,Liu Qing,Li Jing,Shen Yuanyuan,Cheng Jiejun,Guo Shengrong
A novel folate-polyethylene glycol-succinic acid-doxorubicin conjugate (FA-PEG-SA-DOX) micelle loaded with curcumin (CUR) is designed and prepared to target tumor cells via folate-folate receptor interactions and co-deliver chemotherapeutic agent DOX and chemosensitizer CUR for treatment
of multidrug resistant human breast cancer MCF-7/ADR cells. The CUR/FA-PEG-SA-DOX micelles are characterized with the average size of 90.64±0.15 nm and the zeta potential of −15.3±0.8 mV. The CUR and DOX contents of the micelles are 12.07 and 15.69% (w/w), respectively.
The cytotoxicity, cellular uptake and effiux of the micelles are investigated by using MCF-7/ADR cells. The results demonstrate that the CUR/FA-PEG-SA-DOX micelles have greater toxicity (IC50 = 3.10 µg/ml) compared to the free DOX (IC50 = 31.99 µg/ml),
moreover, the micelles present increased cellular uptake and reduced cellular effiux. The combination index of CUR/FA-PEG-SA-DOX micelles was 0.17, which indicate a strong synergistic antitumor efficacy against MCF-7/ADR cells. These results suggest that Curcumin-loaded FA-PEG-SA-DOX micelles
may be a promising nanomedicine for co-delivery dual-drug treatment for cancer.
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