INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2022
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IF 6.51
Tingting Du,Yuchi Wang,Zhiyong Luan,Chaoyue Zhao,Kangjuan Yang
The low immunogenicity and tumor immunosuppressive microenvironment (TIM) are two major obstacles for cancer immunotherapy . Synergistically immunogenic cell death induction and tumor-associated macrophages depletion could perfectly overcome this limitation. Herein, a tumor-associated macrophage (TAMs) membrane-camouflaged pH-responsive doxorubicin (DOX) loaded hyaluronic acid (HA)-g-poly (histidine) polymeric micelles ( [email protected] ) was fabricated for the first time. [email protected] could effectively accumulated into tumor regions via TAMs membrane mediated immune camouflage. In acidic tumor microenvironment , particle size of DHP was enlarged due to decrease hydrophobic interaction of inner core, which caused a “membrane escape effect” to expose inner HA residue. Together high expression of α4β1 integrin , [email protected] could reach CD44/VCAM-1 dual-targetability to facilitate intracellular DOX accumulation for efficient ICD induction. Meanwhile, TAMs membrane could absorb colony stimulating factor 1(CSF1) through high expression of its receptor (CSF1R) on TAMs membrane to deplete TAMs in tumor tissues and relieved TIM. This strategy could efficiently induce cytotoxic T lymphocyte (CTLs) infiltration for antitumor immune response and inhibit tumor progression in 4T1 tumor bearing Balb/c mice. Therefore, [email protected] is suitable for cancer chemotherapy-sensitized immunotherapy.
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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2022
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IF 5.518
Yifei Liu,Xu Guo,Mingwei Zhao,Chenwei Zou,Yeqing Feng,Yining Wu,Caili Dai
The effects of hydrophobic interaction and electrostatic interaction on the structure of zwitterionic wormlike micelles (WLMs) were studied. The change of the hydrocarbon chain length and addition of cetyl trimethyl ammonium chloride (CTAC) were employed to explore the effect of hydrophobic interaction and electrostatic interaction on the wormlike micelles constructed by zwitterionic viscoelastic surfactants and sodium p -toluene sulfonate (NaPts). The experimental results show that increasing hydrocarbon chain length of zwitterionic surfactant and the addition of CTAC can increase the viscoelasticity and zero-shear viscosity of the system. The calculated length of wormlike micelles also increases. This shows that the enhancement of hydrophobic interaction and electrostatic interaction can promote the growth and entanglement of wormlike micelles. In addition, scanning electron microscope (SEM) images confirmed that CTAC makes the connection between the zwitterionic micellar layer closer. This is undoubtedly beneficial to the growth of micellar structure . Finally, this work explores the enhancement mechanism of the hydrophobic interaction and electrostatic interaction on the micelle structure.
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Polymer Chemistry
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2021
·Vol. 13
·期 1
·80-84
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IF 5.582
Wei Chen,Peng Liu
The ultrasound-mediated approach has attracted attention for enhanced localized drug delivery in tumor chemotherapy. Here, well-defined PEGylated dendritic polyurethane (Ph-DPU-PEG) was synthesized as unimolecular micelles with a hydrophobic core via a facile one-pot method for ultrasound-triggered localized drug delivery. The chemotherapeutic drug could be encapsulated in the hydrophobic cores, and the drug-loaded micelles (DOX@Ph-DPU-PEG) were obtained as nanomedicine, which would hardly release the drug without ultrasound, regardless of the acidity of the releasing media. However, they showed an excellent ultrasound-triggered intracellular drug release performance, with a cumulative drug release of 81.6% in the simulated tumor intracellular microenvironment within 12 h. Furthermore, the ultrasound-triggered intracellular drug release was revealed with the CLSM technique and an enhanced tumor growth inhibition was achieved on the HepG2 cells compared to free DOX.
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JOURNAL OF DISPERSION SCIENCE AND TECHNOLOGY
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2021
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IF 2.262
Shanshan Dai,Minmin Tao,Hongsheng Lu
CO2-responsive wormlike micelles based on ionic liquid 1,1,3,3-tetramethylguanidine-oleic acid (TMG-OA) and cationic surfactant tetradecyl trimethyl ammonium bromide (TTAB) was designed in this work, avoiding the volatileness and flammability of traditional wormlike micelles formed with amines. It provides a new method of preparing CO2-switchable wormlike micelles based on ionic liquid with acidic group. The ionic liquid TMG-OA was prepared by the direct neutralization reaction between TMG and HOA at the molar ratio of 1:1. Due to the excellent stability and switchability demonstrated by thermogravimetry (TGA) and pH, TMG-OA can be treated as nonvolatile surfactant with CO2-responsive acidic group. Then the worm-based viscoelastic fluid is formed by the electrostatic interaction between TTAB and TMG-OA, and the steady and dynamic rheology show that the viscoelastic fluid has CO2-switchable thinning behavior. The switchable behavior is consistent with the reversible transition of microstructure from wormlike micelles to emulsion, which were detected by the dynamic light scattering (DLS) and cryo-transmission electron microscope (Cryo-TEM). The microstructural transition is induced by the reversible conversation between TMG-OA component and HOA component upon CO2 and N2/heat.
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ACS Applied Materials & Interfaces
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2020
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IF 8.758
Shengyu Zhang,Ye Gan,Lanlan Shao,Tianqing Liu,Danyi Wei,Yanyan Yu,Hongwei Guo,Hongyan Zhu
Targeting vascular endothelial growth factor (VEGF) using small interfering RNA (siVEGF) has shown great potential in inhibiting the growth, proliferation, and migration of tumors by reducing the proliferation of blood vessels. On the basis of bionic principles, a novel pH-responsive and virus mimetic shell-sheddable chitosan (CS) micelles (CMs) as siRNA delivery system was introduced in this study. The cyclo(Arg-Gly-Asp-d-Phe-Lys) (cRGD) modified poly(enthylene glycol) (PEG) was conjugated to the HA2 modified chitosan via a hydrazone linkage (cRGD-PEG-Hz-CS-HA2). The cRGD-PEG-Hz-CS-HA2 conjugate could form micelles by interacting with the complex of octanal, Boc-l-lysine, and 9-d-arginine (9R) (octyl-Lys-9R) as a hydrophodic core forming agent, termed as cRGD-PEG-Hz-CS-HA2/octyl-Lys-9R (abbreviated as cRGD/HA2/Hz-CMs).The CMs modified with cRGD can accurately target glioma cells (U87MG cells) with high expression of αvβ3. The payloads of siVEGF were packed into the core of cRGD/HA2/Hz-CMs via electrostatic interaction and hydrophobic interaction. The intracellular cargo release was achieved by the pH-responsive lysis of the hydrazone bond in acidic environment of endosome. Moreover, the exposed HA2, as a pH-sensitive membrane-disruptive peptide, assists the escape of the carriers from endosome into cytosol. In addition, cRGD/HA2/Hz-CMs can effectively deliver siVEGF and silence VEGF gene expression in U87MG cells, leading to the significant tumor growth inhibition. This study demonstrates that cRGD/HA2/Hz-CMs can deliver and release siVEGF in a controlled manner, which was traced by the fluorescence resonance energy transfer (FRET) system in order to achieve RNAi-based anti-angiogenic treatment of cancer in vivo.
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DRUG DELIVERY
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2020
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IF 4.902
Xiaojing Xia,Jin Tao,Zhuwa Ji,Chencheng Long,Ying Hu,Zhiying Zhao
The aim of this work is to apply Solutol® HS15 and TPGS to prepare self-assembled micelles loading with ginsenoside Rh2 to increase the solubility of ginsenoside Rh2, hence, improving the antitumor efficacy. Ginsenoside Rh2-mixed micelles (Rh2-M) were prepared by thin film dispersion method. The optimal Rh2-M was characterized by particle size, morphology, and drug encapsulation efficiency. The enhancement of in vivo anti-tumor efficacy of Rh2-M was evaluated by nude mice bearing tumor model. The solubility of Rh2 in self-assembled micelles was increased approximately 150-folds compared to free Rh2. In vitro results demonstrated that the particle size of Rh2-M is 74.72 ± 2.63 nm(PDI = 0.147 ± 0.15), and the morphology of Rh2-M is spherical or spheroid, and the EE% and LE% are 95.27 ± 1.26% and 7.68 ± 1.34%, respectively. The results of in vitro cell uptake and in vivo imaging showed that Rh2-M could not only increase the cell uptake of drugs, but also transport drug to tumor sites, prolonging the retention time. In vitro cytotoxicity and in vivo antitumor results showed that the anti-tumor effect of Rh2 can be effectively improved by Rh2-M. Therefore, Solutol® HS15 and TPGS could be used to entrapping Rh2 into micelles, enhancing solubility and antitumor efficacy.
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JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
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2020
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IF 2.69
Min Wang,Jianghao Zhan,Laijun Xu,Yanjun Wang,Dan Lu,Zhen Li,Jiehua Li,Feng Luo,Hong Tan
Polyurethane nanomicelle is a promising functional drug delivery system. In this work, the polyurethane (P3-PU) was synthesized from PLGA1200-PEG1450-PLGA1200 (P3, a thermosensitive and biodegradable triblock copolymer) and L-lysine ester diisocyanate (LDI). Then, reactive benzaldehyde was further imported to terminate P3-PU to obtain benzaldehyde modified polyurethane (P3-PUDA). The micelles, temperature-sensitive P3-PU nanomicelle and P3-PUDA nanomicelle, were systematically investigated, including the size, stability, temperature sensitivity, drug loading and release behavior, cytotoxic on human hepatocytes (L02), and inhibitory effect on human hepatocellular carcinoma cells (HepG2). The results show the thermosensitive behavior of the micelles can be adjusted by the terminal group. The polyurethane micelles with a uniform size between 20 nm and 30 nm showed excellent stability and good biocompatibility to L02 cells. Besides, in vitro experiments showed that Dox-loaded P3-PUDA micelles exhibited faster and higher release rate at 37 °C and better inhibitory effect on HepG2 than the Dox-loaded P3-PU micelles. Moreover, the achieved benzaldehyde modified polyurethanes also provides various possibilities to adjust further to enlarge its applications. Therefore, the polyurethane micelles will have great potential in the field of drug carriers.
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JOURNAL OF MICROENCAPSULATION
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2020
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IF 2.287
Mingjia Gu,Lidan Lu,Qingxue Wei,Zhiwei Miao,Hang Zhang,Leiping Gao,Lejun Li
Aims This study was designed to prepare chrysophanol-loaded micelles (CLM) to improve the oral bioavailability, targetability and anti-chronic renal failure (CRF) activity of chrysophanol (CH).Methods The preparation of CLM was achieved via thin-film dispersion technique. The in vitro release of CLM compared with free CH was measured in phosphate buffer solution (PBS) containing 0.5%w/v sodium dodecyl sulphate (pH 6.8) while the pharmacokinetic and anti-CRF activity study was also conducted in rats. Moreover, the tissue distribution of CLM was investigated in the mice.Results The CLM had particle size (PS) of 29.64 ± 0.71 nm, and encapsulation efficiency (EE) of 90.48 ± 1.22%w/w. The cumulative release rate of CH from the micellar system was significantly higher than that of the free CH (86%m/m vs. 15%m/m, p < 0.01). In vivo pharmacokinetic studies showed that the bioavailability of CLM after oral administration was substantially improved (about 3.4 times) compared with free drugs (p < 0.01). Also, it was observed that CLM accumulated well in the liver and brain. Moreover, in vitro renal podocytes study showed that CLM had better protection against renal podocyte damage than the free CH. In addition, CLM significantly (p < 0.01) reduced levels of blood urea nitrogen (BUN), kidney injury molecule-1 (Kim-1), and serum creatinine (SCr), which obviously improved kidney damage in rats with CRF.Conclusions Collectively, these findings suggest that mixed micelles may be used as a promising drug delivery system for oral bioavailability improvement and concomitantly enhance the anti-CRF activity of CH, as well as provide a basis for the clinical application of CH.
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CARBOHYDRATE POLYMERS
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2020
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IF 7.182
Feng Shen,Haoquan Zhong,Wenjiao Ge,Junli Ren,Xiaohui Wang
Natural active compounds with antioxidant properties and other potential health benefits, like quercetin (Qu), have aroused wide concern for developing bio-functional products. However, their applications are hindered by their intrinsic poor water solubility and chemical instability. In this paper, a natural antioxidant alpha lipoic acid (ALA) was grafted onto chitosan (CS) to synthesize a novel graft polymer (CS-graft-ALA). In particular, this graft-polymer could self-assemble into spherical nanomicelles in water, with a low critical micelle concentration (CMC) of 0.0076 mg/mL. As a robust and active nanocarrier, the CS-graft-ALA micelles showed high efficiency in encapsulating Qu and dispersing Qu in water. As found, the antioxidant activity of Qu was effectively enhanced when entrapped within CS-graft-ALA micelles. Moreover, CS-graft-ALA micelles could significantly improve the photo-stability and temperature-stability of Qu. The Qu/CS-graft-ALA micelles with excellent water dispersability, stability and improved antioxidant activity hold a great potential for wide applications.
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Drug Delivery and Translational Research
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2020
·Vol. 11
·期 3
·1133-1143
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IF 2.664
Li Ruirui,Shan Linwei,Yao Yanan,Peng Feifei,Jiang Shanshan,Yang Dandan,Ling Guixia,Zhang Peng
The platform of the combination chemo-photodynamic therapy has received widespread attention for enhancing anticancer efficacy and inhibiting tumor growth, which supports thermosensitive and controlled drug release. Here, an injectable thermoreversible hydrogel (BPNSs/DTX-M-hydrogel) co-encapsulating black phosphorus nanosheets (BPNSs) and docetaxel (DTX) micelles was prepared to increase drug accumulation in tumor tissue and improve anticancer efficacy. BPNSs were prepared by liquid exfoliation method with a simple and rapid preparation, and DTX micelles were prepared by the thin film dispersion method. Hydrogel was prepared with F127 as hydrogel matrix for intratumoral injection. BPNSs, DTX micelles, and BPNSs/DTX-M-hydrogel were characterized by particle size, morphology, stability and degradation, phase transition feature, and photodynamic performance. And the in vivo anticancer efficacy was evaluated in 4T1 tumor-bearing Balb/c mice. The results showed that the particle size of DTX micelles and BPNSs were about 16 and 180 nm, respectively. The hydrogel with the transformation temperature at near body exhibited great photodynamic efficacy and good biodegradability. Moreover, BPNSs/DTX-M-hydrogel with the combination of chemotherapy and photodynamic therapy exhibited unique anticancer efficacy with low toxicity. In conclusion, the combination platform of chemo-photodynamic therapy based on BPNSs could be a prospective strategy in antitumor research.
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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.
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BIOMATERIALS
·
2020
·
IF 10.317
Jinsong Tao,Zhengjie Wei,Yuan He,Xingyang Yan,Simon Ming-Yuen Lee,Xueqing Wang,Wei Ge,Ying Zheng
Understanding the behaviors of nanomedicines in vivo is one of the most important prerequisites for the design and optimization of nanomedicines. However, the in vivo tracking of nanomedicines in rodents is severely limited by the restricted imaging possibilities within these animals. To meet these needs, the FRET (fluorescence or Förster resonance energy transfer) imaging combined with visual zebrafish larvae model (7 dpf) was used to study the behaviors of polymeric micelles in vivo at high spatiotemporal resolution . Firstly, the FRET ordinary Pluronic micelles (OPMs) and disulfide bond crosslinked Pluronic micelles (CPMs) were synthesized to quantify their integrity in vitro and in vivo by FRET ratio. The behaviors and integrity of OPMs and CPMs in vivo were visually investigated in zebrafish larvae across the entire living organism and at cellular molecular level after intravenous microinjection . Results showed that OPMs were rapidly disassociated in circulation, then largely sequestrated by the endothelial cells (ECs) of caudal vein (CV) and liver in zebrafish larvae, which resulted in quick elimination from blood circulation. While the CPMs were more stable and escaped the sequestration by ECs of CV and liver, which prolonged their circulation in blood. Moreover, we pioneered to use the zebrafish model to reveal that polymeric micelles were eliminated through hepatobiliary pathway after disassociation. While the intact micelles were relatively difficult to eliminate. We further verified that the scavenger receptors of ECs but not the macrophages mainly mediated the elimination of polymeric micelles in CV and liver of zebrafish larvae. These finding on behaviors and elimination mechanisms of polymeric micelles in zebrafish model could contribute to the rational design and optimization of nanomedicines, further guide their studies in rodents.
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