EUROPEAN POLYMER JOURNAL
·
2022
·
IF 5.546
Jinying Wang,Jiannan Cheng,Kai Tu,Yuxue Wang,Qing Yu,Lifen Zhang,Zhenping Cheng
In this work, based on the semifluorinated macro-RAFT (reversible addition-fragmentation chain transfer) agent and polymerization-induced self-assembly (PISA) strategy, we established a mild and facile method to prepare reversed micelles up to 40 wt% of solid content with main-chain-type semifluorinated alternating copolymer as shell and hydrophilic polymer as core for the first time. The fluorinated macro-RAFT agent was synthesized by combination of step transfer-addition & radical-termination (START) polymerization and post-modification method. The reversed micelles were generated by the PISA of N,N -dimethacrylamide (DMA) in the presence of the fluorinated macro-RAFT agent in the non-polar solvent toluene at 70 °C, and fluorinated reversed micelles can be fixed in the presence of crosslinker ethyleneglycol dimethacrylate (EGDMA). This strategy will facilitate to open a new way in designing novel functional synthetic fluorinated nanomaterials.
研究领域:
高分子科学
·
材料化学
·
纳米技术
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DOI
高影响因子
Molecular Therapy-Nucleic Acids
·
2021
·
IF 8.886
Jing Miao,Xiqin Yang,Xuwei Shang,Zhe Gao,Qian Li,Yun Hong,Jiaying Wu,Tingting Meng,Hong Yuan,Fuqiang Hu
Hepatitis B (HB) is a viral infectious disease that seriously endangers human health, and since there are no radical drugs to counter this, effective and safe therapies urgently need to be developed. HB virus (HBV) mainly infects hepatocytes (HCs), while the drugs are easily phagocytosed by Kupffer cells (KCs). In this study, the glutathione concentration difference between HCs and KCs was examined and utilized in an ideal drug-release strategy. Here, galactosylated chitosan-oligosaccharide-SS-octadecylamine (Gal-CSSO) was prepared to accurately deliver 10-23 DNAzyme DrzBC (blocking HBeAg expression) or DrzBS (blocking HBsAg expression) in targeted HB therapy. In vitro Gal-CSSO systems exhibited low cytotoxicity, endosomal escape, and glutathione responsiveness. The HBeAg and HBsAg secretion of HepG2.2.15 was significantly decreased by Gal-CSSO systems, and the maximum inhibition rates were 1.82-fold and 2.38-fold greater than those of commercial Lipofectamine 2000 (Lipo2000) systems. In vivo Gal-CSSO systems exhibited HC targeting and HC microenvironmental responsiveness without noticeable hepatotoxicity or systemic toxicity. The HBeAg and HBsAg titers of the HBV-infected mice were evidently decreased by Gal-CSSO systems, and the inhibition rates were 1.52-fold and 1.22-fold greater than those of Lipo2000 systems. This study presents a kind of glycolipid-like polymer micelles that promise efficient and safe gene therapy of HB.
研究领域:
药理学
·
分子生物学
·
治疗学
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DOI
PubMed
高影响因子
MACROMOLECULAR BIOSCIENCE
·
2017
·Vol. 17
·期 8
·1700114
·
IF 3.238
Ting Wu,Longhai Wang,Shenggang Ding,Yezi You
A novel PEGylation polypeptide, poly(ethylene glycol)- b -poly( l -lysine)- b -poly( l -cysteine) (PEG-PLL-PCys) triblock copolymer is synthesized via the sequential ring-opening polymerization of amino acid N -carboxyanhydrides initiated by methoxypolyethylene glycol amine (mPEG-NH 2 , M w is 2 kDa). Subsequently, the obtained polypeptide is partially conjugated with fluorocarbon chains via disulfide exchange reaction. PLL segment can condense plasmid DNA through an electrostatic force to form a complex core, PEG segment surrounding the complex like a corona can prevent the complex from precipitation and reduce the adsorption of serum, while PCys segment with fluorocarbon can enhance the cellular uptake and the stability of the formed polyplex micelles in physiological conditions. Experiment results exhibit that the fluorinated polypeptides have low cytotoxicity and good gene transfection efficiency even in the presence of 50% fetal bovine serum.
研究领域:
高分子化学
·
药学
·
生物医学工程
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2017
·
IF 7.504
Danni Ran,Jiani Mao,Changyou Zhan,Cao Xie,Huitong Ruan,Man Ying,Jianfen Zhou,Wan-Liang Lu,Weiyue Lu
Compared to that of other tumors, various barriers, such as the blood–brain barrier (BBB), enzymatic barriers, and the blood–brain tumor barrier, severely impede the successful treatment of gliomas. Peptide ligands were frequently used as targeting moieties to mediate brain tumor-targeted drug delivery. LWSW (SYPGWSW) is a recently reported quorum-sensing (QS) peptide that is able to efficiently cross the BBB. Even though linear LWSW traverses the BBB in vitro, its in vivo targeting ability has been greatly impaired due to proteolysis. Here, we developed a stable peptide, DWSW (DWDSDWDGDPDYDS), using the retro-inverso isomerization technique to achieve an enhanced antiglioma effect. In vitro studies have demonstrated that both the LWSW and DWSW peptides possessed excellent tumor-homing properties and barrier-penetration abilities, whereas DWSW exhibited exceptional stability in serum and maintained its targeting ability after serum preincubation. In vivo, DWSW-modified probes and micelles accumulated more efficiently in the glioma region in comparison with LWSW-modified probes and micelles because of full resistance to proteolysis in blood circulation. As expected, DWSW-modified paclitaxel (PTX)-loaded micelles (DWSW Micelle/PTX) exhibited the longest median survival time among glioma-bearing nude mice. Our results suggested that the QS peptide appears to be a promising targeting moiety, with potential applications in glioma-targeted drug delivery.
研究领域:
药学科学
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神经科学
·
癌症研究
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药物递送系统
·
生物医学工程
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DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2017
·
IF 7.786
You Li,Man Li,Tao Gong,Zhirong Zhang,Xun Sun
Increasing attention has been paid to nasal delivery. Subunit vaccines based on antigenic proteins or polypeptides offer good safety. However, lack of delivery efficiency, particularly for nasal immunization, is a big issue. Here we designed a highly tunable polymeric hybrid micelle (PHM) system offering good vaccine efficacy after nasal administration . PHMs are formulated from two amphiphilic diblock copolymers , polycaprolactone-polyethylenimine (PCL-PEI) and polycaprolactone-polyethyleneglycol (PCL-PEG), the ratio of which determines PHM physicochemical properties. Citraconic anhydride-modified ovalbumin (Cit-OVA), as model antigen, was incorporated into PHMs via electrostatic interaction , giving antigen-loaded micelles of around 150 nm in size. Their surface characteristics which are found closely related to their in vivo kinetics can be modulated by adjusting the mass ratio of PCL-PEG and PCL-PEI. PHM/Cit-OVA complexes containing PCL-PEI and PCL-PEG in a 1:1 mass ratio induced strong immune responses in nasal mucosa and serum in vivo without causing obvious toxicity, and Cit-OVA was efficiently internalized by dendritic cells. These results demonstrate the promise of this multifunctional polymeric delivery system for nasal vaccination.
研究领域:
药学
·
免疫学
·
纳米技术
·
疫苗学
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DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2020
·
IF 6.092
Xiqin Yang,Tong Yu,Yingping Zeng,Keke Lian,Xueqing Zhou,Jia Ke,Yinghong Li,Hong Yuan,Fuqiang Hu
Lymph nodes are proposed as the intriguing target in cancer immunotherapy, and cellular immunity is vital for vaccines to fight against cancer. However, inefficient delivery of vaccines to lymph nodes and deficient lysosomal escape of antigens result in weak cellular immunity, which restrains the strength of vaccines in inducing antitumor immune responses. Hence, dendritic cell membrane (DCM)/histidine-modified stearic acid-grafted chitosan (HCtSA)/ovalbumin (OVA) micelles, as pH-responsive biomimetic vaccines, were fabricated to target lymph nodes and induce cellular immunity for enhanced antitumor immune responses. DCM/HCtSA/OVA micelles exhibited pH-dependent antigen release behavior, which resulted in efficient escape of antigens from dendritic cell (DC) lysosomes. Besides, DCM/HCtSA/OVA micelles accumulated and reserved in the lymph nodes, which ensured effective uptake by DCs. Importantly, DCM/HCtSA/OVA micelles induced potent T cell immune responses, promoted secretion of antitumor-related cytokines, and notably inhibited tumor growth. Overall, DCM/HCtSA/OVA micelles exhibit great potential in targeted immunotherapy and can provide guidance for the design of vaccines.
研究领域:
肿瘤免疫学
·
纳米医学
·
生物材料
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DOI
高影响因子
EUROPEAN POLYMER JOURNAL
·
2023
·
IF 6
Peiyun Cheng,Na Liang,Wei Zhao,Xianfeng Gong,Weijia Wang,Shaoping Sun
In this study, an amphiphilic polymer mPEG-CS-Bio-Hz-Q with capabilities of near-infrared (NIR) fluorescence imaging, active tumor targeting, minimized protein adsorption and pH-responsive drug release was designed and synthesized. The polymer was served as a micellar carrier for paclitaxel (PTX) delivery. The mean size of PTX-loaded mPEG-CS-Bio-Hz-Q micelles was 123.5 nm. In vitro drug release study indicated the pH-triggered PTX release behavior of the micelles. Cellular uptake study demonstrated that the micelles could be effectively internalized by MCF-7 cells and exhibit bright fluorescence. In vivo investigation illustrated the high antitumor activity and excellent safety of the micelles. The mPEG-CS-Bio-Hz-Q micellar system would be promising candidate for bioimaging and cancer therapy.
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产品关联
DOI
高影响因子
Biomaterials Science
·
2023
·Vol. 11
·期 14
·4890-4906
·
IF 6.6
Jianhao Liu,Xiaoman Xu,Yanying Li,Jingxia Xu,Ruogang Zhao,Siwei Liu,Jingliang Wu,Li Zhang,Bo Zhang
Comprehensively regulating the TME is now regarded as a promising approach for cancer treatment. Herein, a novel “three-in-one” effect is presented for simultaneously killing tumor cells, inhibiting the EMT of CAFs, and improving immune responses. In this study, bortezomib (BTZ) is selected for the treatment of breast cancer; it has multiple pharmacological mechanisms for killing tumor cells through the NF-κB signaling pathway, inhibiting the activity of CAFs by activating caspase-3, and enhancing the function of CD8+ T cells by regulating the expression of immune-stimulating factors. To improve the druggability of BTZ in solid tumors, BTZ-loaded lipid/glycocholic acid mixed micelles (BTZ-LGs) were prepared to verify the “three-in-one” effect in killing tumor cells, inhibiting CAFs, and improving immune responses. In the present work, BTZ-LGs were verified to show enhanced in vitro cytotoxicity in both 4T1 cells and 4T1/NIH3T3 co-cultured cells, as well as a superior in vivo treatment effect in different tumor-bearing mouse models. Additionally, BTZ-LGs could regulate the expression of α-SMA, caspase-3, E-cadherin, and N-cadherin, indicating their good inhibiting ability on both tumor cells and CAFs. More importantly, immunological analysis revealed that BTZ-LGs promoted the expression of the immunostimulatory factor IL-2 in tumor tissues, activated anti-tumor T cells, and overcame tumor-induced CD8+ T cell dysfunction. All these findings suggest that BTZ-LGs can achieve a “three-in-one” effect in terms of killing tumor cells, suppressing CAFs, and improving immune responses. This simple and multi-effective therapeutic strategy offers a promising approach for cancer therapy.
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2023
·
IF 5.8
Jingmou Yu,Liangliang Wang,Yun Ling,Xin Xiao,Juntao Gong,Hongguang Jin,Jing Xu,Pu Chen,Xin Xie,Lei Zhang
Triple-negative breast cancer is an offensive tumor that is highly challenging to cure. In this study, we developed novel polymeric nanoparticles that target dual receptors and respond to reducing conditions for chemotherapeutic drug release in the treatment of triple-negative breast cancer. Then we synthesized and characterized a targeted peptide-grafted chondroitin sulfate A-ss-deoxycholic acid (TCSSD) copolymer and prepare doxorubicin (DOX)-loaded TCSSD (TCSSD-D) micelles high-loading content. The bioresponsive drug release of TCSSD-D nanoparticles was demonstrated in a glutathione-containing phosphate buffer solution . We found that TCSSD-D effectively targeted CD44 and P-selectin receptors both in vitro and in vivo . TCSSD-D micelles were higher cytotoxicity and cellular uptake than unmodified DOX-containing micelles in MDA-MB-231 cells. Furthermore, TCSSD-D micelles showed the strongest suppression of tumor growth among three DOX-based formulations in triple-negative MDA-MB-231-bearing nude mice . These results suggest that amphiphilic TCSSD nanoparticles can serve as a targeted and intelligent delivery vehicle for triple-negative breast cancer therapy.
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2022
·
IF 10.723
Xue Zhang,Xueya Xu,Xiaoying Wang,Yajuan Lin,Yaling Zheng,Wen Xu,Jian Liu,Wei Xu
A glycyrrhetinic acid-modified carboxymethyl chitosan-thioketal-rhein (GCTR) conjugate was designed and synthesized for the in vivo delivery of celastrol (Cela). Cela was encapsulated into polymeric micelles (PMs) formed by GCTR conjugates self-assembly in water to form Cela/GCTR PMs with high drug loading capacity and small particle size. Cela/GCTR PMs had a sustained-release characteristic in the blood environment and a rapid-release feature in the tumor microenvironment. Cela/GCTR PMs had a significant proliferation inhibitory effect on HepG2 and BEL-7402 cells, but a negligible impact on L-02 cells at low concentrations. Cela/GCTR PMs possessed reactive oxygen species (ROS)-responsive properties in vitro and in cells, could improve the bioavailability of Cela, and exert remarkable hepatoma-targeting properties. Cela/GCTR PMs could also effectively inhibit tumor growth with no apparent damage to different organs. In summary, GCTR PMs with good ROS-responsive and hepatoma-targeting properties are expected to be possible delivery carriers for hydrophobic antineoplastic drugs for hepatocellular carcinoma therapy.
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Wei Xu,Honglan Wang,Lihui Dong,Pan Zhang,Yan Mu,Xueyan Cui,Jianping Zhou,Meirong Huo,Tingjie Yin
Introduction: Herein, a hyaluronic acid (HA)-coated redox-sensitive chitosan-based nanoparticle, HA(HECS-ss-OA)/GA, was successfully developed for tumor-specific intracellular rapid delivery of gambogic acid (GA).Materials and methods: The redox-sensitive polymer, HECS-ss-OA, was prepared through a well-controlled synthesis procedure with a satisfactory reproducibility and stable resulted surface properties of the assembled cationic micelles. GA was solubilized into the inner core of HECS-ss-OA micelles, while HA was employed to coat outside HECS-ss-OA/GA for CD44-mediated active targeting along with protection from cation-associated in vivo defects. The desirable redox-sensitivity of HA(HECS-ss-OA)/GA was demonstrated by morphology and particle size changes alongside in vitro drug release of nanoparticles in different simulated reducing environments.Results: The results of flow cytometry and confocal microscopy confirmed the HA-receptor mediated cellular uptake and burst drug release in highly reducing cytosol of HA(HECS-ss-OA)/GA. Consequently, HA(HECS-ss-OA)/GA showed the highest apoptosis induction and cytotoxicity over the non-sensitive (HA(HECS-cc-OA)/GA) and HA un-coated (HECS-ss-OA/GA) controls against A549 NSCLC model both in vitro and in vivo. Furthermore, a diminished systemic cytotoxicity was observed in HA(HECS-ss-OA)/GA treated mice compared with those treated by HA un-coated cationic ones and GA solution.
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产品关联
DOI
PubMed
高影响因子
Polymer Chemistry
·
2023
·Vol. 14
·期 7
·888-897
·
IF 4.6
Yuting Min,Ruizhen Zhang,Xuli Dong,Lifang Zhang,Dongming Qi,Zan Hua,Tao Chen
A well-defined triblock light-responsive amphiphilic copolymer with nitrospiropyran as the middle block was prepared by reversible addition–fragmentation chain transfer (RAFT) polymerization. The polymeric micelles obtained by self-assembling of the copolymer in water exhibited reversible size changes upon ultraviolet (UV) and visible (Vis)-light irradiation, owing to the transition between the closed three-dimensional spiropyran (SP) and the open planar merocyanine (MC) form, and the corresponding transformation of hydrophobicity and hydrophilicity. The hydrophobic SP form of nitrospiropyran resulted in a larger core diameter, showing higher dye adsorption ability in methyl red adsorption experiments. Upon UV irradiation, the transition of SP to hydrophilic MC caused a decrease of the core diameter, displaying a higher catalytic reaction rate in the Knoevenagel condensation reaction when base-functionalized micelles were applied. This work presented facile light-regulated reversible size changes of polymeric micelles. We expect that the light-regulated strategy developed here would be useful in the fabrication of smart nanoreactors for dye adsorption, catalysis, etc. in a controllable manner.
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）