INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2022
·
IF 8.025
Jinghui Wang,Xiaoyu Liu,Yanqin Wang,Meiwen An,Yubo Fan
Excellent mechanical and tissue adhesive properties, long-lasting environmental suitability and reliable biocompatibility are essential factors for the hydrogels to be applied as wound dressing in the clinical fields. Based on the self-assembly micelle structures, a new type of casein micelles (CEs)/polyvinyl alcohol (PVA) GW (glycerol-water) organohydrogel was designed and synthesized by a simple one-pot method. Through a unique “load sharing” effect, the CEs which own suitable adhesion abilities and drug loading capacities simultaneously were embedded into the PVA networks by rich hydrogen bonds, so that to obtain the composite organ hydrogel with not only excellent adhesive abilities, but also enhanced mechanical properties. Benefited from the unique GW binary solvent system, the organohydrogel showed long-lasting moisture lock-in capacity and extreme temperature tolerance (in the range of ‐−20 °C ~ 60 °C). Particularly, after loading the model antibacterial drugs (allicin) within the CEs, the as-developed CEs/PVA GW gel exhibited a prominent long-lasting (>100 h) antibacterial properties (>90%). Furthermore, the organohydrogel was confirmed with prominent biocompatibility to support fibroblast cell proliferation and migration. This work proposed a new strategy to build CEs-based gel system, which have a great potential application in terms of prevent bacterial infection, accelerate tissue proliferation and wound healing.
研究领域:
材料科学
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生物医学工程
·
组织工程
·
伤口愈合
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2022
·Vol. 23
·期 17
·9698
·
IF 6.208
Dong Wan,Yujun Liu,Xinhao Guo,Jianxin Zhang,Jie Pan
To endow the polymeric prodrug with smart properties through a safe and simple method, matrix metalloproteinase (MMPs) responsive peptide GPLGVRGDG was introduced into the block copolymer to prepare TPGS3350-GPLGVRGDG-DOX&DOX micelles, where TPGS3350is D-α-tocopheryl polyethylene glycol 3350 succinate. During the doxorubicin delivery, the cleavage of the peptide chain triggers de-PEGylation, and the remaining VRGDG sequence was retained on the surface of the micelles, which can act as a ligand to facilitate cell uptake. Moreover, the cytotoxicity of TPGS3350-GPLGVRGDG-DOX&DOX micelles against 4T1 cells was significantly improved, compared with TPGS3350-GPLGVRG-DOX&DOX micelles and TPGS3350-DOX&DOX micelles. During in vivo studies, TPGS3350-GPLGVRGDG-DOX&DOX micelles exhibited good anticancer efficacy with long circulation in the body and more efficient accumulation at the tumor site. Therefore, TPGS3350-GPLGVRGDG-DOX&DOX micelles have improved antitumor activity and reduced toxic side effects. This work opens new potential for exploring the strategy of drug delivery in clinical applications.Keywords:drug delivery;peptide;micelles
研究领域:
药学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Yao Li,Jie Wang,Yaru Li,Jiajia Luo,Fang Liu,Tiantian Chen,Yuting Ji,Hong Yang,Zheng Wang,Yanjun Zhao
As a clinical unmet need, uncontrolled inflammation is characterized by the crosstalk between oxidative stress and an inflammatory response. Ferroptotic cell death plays an essential role in uncontrolled inflammation. Hence ferroptosis inhibition is capable of managing hyper-inflammation, but the small molecular inhibitors show poor residence in cell membranes. The plasma membrane is the major site of lipid peroxidation that is the key event of ferroptosis. To address such a challenge, chiral radical trapping polymers were engineered by mimicking the structure of the cell membrane with imbedded helical proteins. The polymers were tailored to show an α-helix conformation that enabled increased hydrophobicity, prolonged membrane retention, and enhanced lipid radical trapping. The chiral polymers are amphiphilic, and the self-assembled micelles exhibited an extended blood circulation. At the lipopolysaccharide-induced macrophage and mice models, chiral polymer micelles effectively suppressed ferroptosis and repressed inflammatory cytokines. The current work provides an innovative means for attenuating uncontrolled inflammation by anti-ferroptotic polymer micelles.
研究领域:
药理学
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材料科学
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炎症研究
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纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LANGMUIR
·
2023
·
IF 3.9
Yanjie Xu,Xuefeng Liu
How to fabricate multiresponse worm-like micelles (WLMs) and the corresponding green disposal is still challenging. A strategy of fabricating the surfactant-based WLMs that can respond simultaneously to light, heat, and pH was developed by using triple-response sodium (E)-2-(4-(phenyldiazenyl)phenoxy) acetate (AzoNa) and butyrylcholinesterase (BChE)-hydrolyzable palmitoylcholine bromide (PCB). Under the optimal molar ratio of AzoNa to PCB (∼0.5), the PCB-AzoNa WLMs formed with a maximum zero-shear viscosity (η0) value of about 2.1 × 105 mPa·s and an average diameter (D) of 4.1 ± 0.6 nm under conditions of 37 °C and pH 7.4. After irradiated with 365 nm UV light for 80 min, AzoNa underwent the trans-to-cis transition, by which the PCB-AzoNa WLMs was destroyed; however, the PCB-AzoNa WLMs could be reformed upon the irradiation of 455 nm blue light for 18 h or heating at 70 °C for 45 min due to the cis-to-trans isomerization of AzoNa. When pH changed from 7.4 to 2.0, the PCB-AzoNa WLMs was destroyed rapidly because of the conversion of AzoNa to the acid form of AzoH, whereas the PCB-AzoNa WLMs could be reformed after pH was restored to 7.4. The multiple responsiveness of the PCB-AzoNa WLMs was reversible due to the reversible trans–cis isomerization or protonation of AzoNa. Besides, the average D values of light, heat, and pH-regenerated PCB-AzoNa WLMs were 4.2 ± 0.7, 4.0 ± 0.7, and 4.0 ± 0.6 nm, respectively. Finally, the PCB-AzoNa WLMs could be enzymatically disorganized under conditions of 37 °C and pH 7.4 due to the BChE-catalyzed hydrolysis of PCB. We hope that the fabrication and enzymatic disorganization strategies for PCB-based multiresponse WLMs presented here will find potential applications in the formulation of antimicrobial household and personal care products containing PCB and in the green disposal of viscous waste containing PCB.
研究领域:
材料科学
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生物化学
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环境科学
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Lan Tang,Wenhui Jiang,Lan Wu,Xiaolan Yu,Zheng He,Weiguang Shan,Lulu Fu,Zhenhai Zhang,Yunchun Zhao
Background Doxorubicin (DOX) is an anthracycline antibiotic that inhibits the growth of several solid and hematologic malignant tumors. Increasing the targeting ability of DOX and reducing the multi-drug resistance (MDR) of tumor cells to DOX are major aims for researchers.Purpose In this study, to increase therapeutic efficiency, reduce the side effects and the MDR of tumor cells to DOX, D-alpha-tocopheryl polyethylene glycol 2000 succinate monoester (TPGS2000)-DOX prodrug micelles were developed by grafting DOX to TPGS2000 via an amide bond that release DOX in the slightly acidic conditions in tumor tissue.Materials and Methods The TPGS2000-DOX micelles were constructed using polyethylene glycol 12-hydroxy stearate (Solutol HS15) as the carrier. The in vitro drug release profile and dilution stability of the nanomicelles were determined. The in vitro cytotoxicity and distribution of the nanomicelles in the tumor cells were also investigated. Moreover, we explored the therapeutic outcomes using the MCF-7/ADR tumor-bearing murine model.Results The average particle size was approximately 30 nm with a narrow distribution, which was conducive for solid tumor accumulation. The results of in vivo imaging and in vitro cellular uptake assays demonstrated that the TPGS2000-DOX micelles increased the tumor-targeting ability and cellular uptake of DOX. The anticancer potential of TPGS2000-DOX micelles was higher than that of DOX, as revealed by in vitro cytotoxic assays with MCF-7/ADR cells and in vivo antitumor assays with MCF-7 tumor-bearing nude mice.Conclusion TPGS2000-DOX prodrug micelles reverse the MDR of tumor cells, achieve passive targeting by forming nanomicelles, and subsequently enhance the efficacy and reduce the toxicity of DOX.
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
ACS Applied Bio Materials
·
2020
·
IF 0
Dong Wan,Chao Li,Jie Pan
In order to overcome the deficiencies of conventional nanotechnology-based drug delivery systems such as a short circulation time in blood, lack of tumor targeting, slow drug release in the interior of cancer cells, and so on, reduction-responsive polymeric micelles developed in this study with copolymers of TPGS3350-SS-DTX and TPGS3350-folate were triggered for cancer-targeted drug delivery. The layer of TPGS3350 in micelles was used to stabilize micelles and enhance the circulation period of micelles in blood. Once the micelles accumulated at the tumor region by EPR effect, tumor cells could ingest these micelles by the pathway of folate-receptor-mediated endocytosis. Next, fast drug release in cancer cells was achieved under the effect of high level of glutathione (GSH) inside cancer cells. The micelles invented in this study demonstrated various functions comprising active targeting, extended circulating life in blood, fast intracellular drug release, and so on. It can be noticed from findings in this research that these cooperative functions in micelles could significantly promote chemotherapeutic effectiveness and reduce their toxic side effects. Moreover, this work provides a drug delivery strategy to explore the feasibility of application reduction-responsive micelles for chemotherapy in clinic.
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
DOI
JOURNAL OF CONTROLLED RELEASE
·
2021
·
IF 9.776
Xingyue Yang,Qian Qiu,Gengqi Liu,He Ren,Xiaojie Wang,Jonathan F. Lovell,Yumiao Zhang
Effective delivery of antimicrobial agents to intracellular pathogens represents a major bottleneck for a wide variety of infectious diseases. To address this, we developed SIR-micelles(+), as a new delivery vehicle comprising antibiotic-loaded micelles with rapid self-immolation within cells for targeted delivery to macrophages, where most intracellular bacterial reside. After phagocytosis, SIR-micelles(+) rapidly release the pristine antibiotic after the cleavage of the disulfide bonds by intracellular reducing agents such as glutathione (GSH). Colistin , a hydrophilic and potent “last-resort” antibiotic used for the treatment of drug-resistant bacterial infection, was encapsulated in SIR-micelles with 40% yield and good short-term storage stability. Hydrophobic moieties and mannose ligands in SIR-micelles(+) enhanced the delivery of colistin into macrophages. The traceless and thiol-responsive release of colistin effectively eliminated intracellular Escherichia coli within twenty minutes. In a murine pneumonia model, SIR-micelles(+) significantly reduced bacterial lung burden of multidrug-resistant Klebsiella pneumoniae . Furthermore, SIR-micelles(+) improved the survival rate and reduced the bacterial burden of organs infected by intracellular bacteria transferred from donor mice. Using this formulation approach, the nephrotoxicity and neurotoxicity induced by antibiotic were reduced by about 5– 15 fold. Thus, SIR-micelles(+) represent a new class of material that can be used for targeting treatment of intracellular and drug-resistant pathogens.
研究领域:
药学
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感染性疾病
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纳米技术
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE
·
2015
·Vol. 26
·期 11
·1-13
·
IF 2.587
Wu Yukun,Yang Chengling,Lai Quanyong,Zhang Qian,Wang Wei,Yuan Zhi
To ideally solve the contradiction between enhanced cellular uptake and prolonged blood circulation, reversible targeting polymeric micelles based on the expanding and shrinking behavior of a temperature-responsive polymer were developed. The micelle contained a hydrophobic PCL core and a mixed shell consisting of poly( N -isopropylacrylamide) (PNIPAAm) and biotin-terminated poly(ethylene glycol) (Biotin-PEG), and its targeting ability could be switched on/off by temperature. The cellular uptake of the complex polymeric micelles was studied. The results from a quantitative enzyme-linked immunosorbent assay (ELISA) indicated that the surface biotin content increased by as much as 11.6-fold when the temperature increased above the lower critical solution temperature (LCST). More importantly, the ELISA confirmed that biotin-mediated targeting on the surface was reversibly switched on and off for at least five cycles. In addition, the results from quantitative flow cytometry and confocal spectroscopy indicated that the cellular uptake of the targeted micelles at temperatures above the LCST was much higher than that at temperatures below the LCST. This complex polymeric micelle with reversible targeting property could be a promising alternative for drug delivery.
研究领域:
药剂学
·
生物材料学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2016
·Vol. 4
·期 31
·5256-5264
·
IF 4.872
Guanglong Ma,Weifeng Lin,Zhen Wang,Juan Zhang,Haofeng Qian,Liangbo Xu,Zhefan Yuan,Shengfu Chen
Protein molecules, which typically have a hydrophobic core and a zwitterionic shell with a polypeptide backbone, could be ideal materials for nanodrug vehicles (NDVs) with low side effects. Here, we synthesized poly(L-aspartic acid(lysine))-b-poly(L-lysine(Z)) (PAsp(Lys)-b-PLys(Z)) (PALLZ), a novel amphiphilic block polypeptide with key structures of protein to investigate the possibility for use as a NDV. This polypeptide can spontaneously self-assemble into micelles in aqueous solution with a zwitterionic brush (the PAsp(Lys) part) to provide the nonfouling shell and a hydrophobic core (the PLys(Z) part) for loading hydrophobic drugs. The doxorubicin (DOX) loaded PALLZ micelles showed excellent resistance to nonspecific protein adsorption in FBS, which leads to very low internalization. Moreover, PALLZ micelles showed no cytotoxicity to MCF7, HeLa and HepG-2 cells up to 500 μg mL−1. All these results indicated that zwitterionic amphiphilic block polypeptides could be promising materials for NDVs.
研究领域:
生物材料学
·
药物递送系统
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
COLLOID AND POLYMER SCIENCE
·
2016
·Vol. 295
·期 1
·1-12
·
IF 1.89
Qi Peilan,Bu Yongqiang,Xu Jing,Qin Benkai,Luan Shujuan,Song Shiyong
Many tumor cells have acidic microenvironment that can be exploited for the design of pH-responsive drug delivery systems. In this work, well-defined pH-sensitive and biodegradable polymeric micelles were prepared and evaluate as carrier of paclitaxel (PTX). A diblock copolymer constituting of a poly(ethylene glycol) (PEG) and a polycaprolactone (PCL) segment linked by a pH-sensitive hydrazone bond (Hyd), which was denoted as mPEG-Hyd-PCL, was synthesized. The copolymer was assembled to micelles with mean diameters about 100 nm. The mean diameters and size distribution of the hydrazone-containing micelles increased obviously in mildly acidic environments while kept unchanged in the neutral. No significant change in size was found on polymeric micelles without hydrazone (mPEG-PCL). PTX was loaded into micelles, and the anticancer drug released from mPEG-Hyd-PCL micelles was promoted by the increased acidity. In vitro cytotoxicity study showed that the PTX-loaded mPEG-Hyd-PCL micelles exhibited significantly enhanced cytotoxicity against HepG2 cells compared to the non-sensitive mPEG-PCL micelles. These results suggest that hydrazone-containing copolymer micelles with pH sensitivity and biodegradability show excellent potential as carriers of anticancer drugs.
研究领域:
药剂学
·
肿瘤学
·
生物材料学
✓ 已验证
DOI
高影响因子
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2019
·
IF 2.367
Yu-Jiao Xie,Qi-Long Wang,Michael Adu-Frimpong,Jian Liu,Kang-Yi Zhang,Xi-Ming Xu,Jiang-Nan Yu
Isoliquiritigenin (ISL) possesses a variety of pharmacological activities amid poor solubility in water which has restricted its clinical application. In this study, isoliquiritigenin-loaded F127/P123 polymeric micelles (ISL-FPM) were successfully prepared and evaluated in vitro and in vivo. The particle size, polydispersity index, and zeta potential of the selected formulation were 20.12 ± 0.72 nm, 0.183 ± 0.046, and −38.31 ± 0.33 mV, respectively, coupled with high encapsulation efficiency of 93.76 ± 0.31%. Drug-loading test showed the solubility of ISL after formulating into micelles was 232 times higher than its intrinsic solubility. Moreover, critical micelle concentration (CMC) was tested with fluorescence probe method and turned out to be quite low, which implied high stability of ISL-FPM. Release profile in HCl (pH 1.2), double distilled water, and PBS (pH 7.4) of ISL-FPM reached over 80%, while free ISL was around 40%. Pharmacokinetic research revealed that formulated ISL-FPM significantly increased bioavailability by nearly 2.23-fold compared to free ISL. According to the results of in vitro antioxidant activity, scavenging DPPH activity of ISL was significantly strengthened when it was loaded into polymeric micelles. Altogether, ISL-FPM can act as a promising approach to improve solubility as well as enhance bioavailability and antioxidant activity of ISL.
研究领域:
药剂学
·
药物化学
✓ 已验证
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2016
·
IF 3.902
Jianfeng Wang,Xiaomin Zhang,Yixin Cen,Xianfu Lin,Qi Wu
Gemcitabine is an important pyrimidine antimetabolite that inhibits cellular DNA synthesis. However, the therapeutic efficacy and clinical benefit of gemcitabine are severely compromised due to its rapid plasma metabolism and low selectivity towards tumor tissues. To overcome these limitations, we prepared novel PEGylated gemcitabine-contained comb-like copolymers poly(monomethoxyl PEG 350 methylacrylate ⿿ co - 5⿲-O-vinyladipyl- gemcitabine) (poly(mPEG 350 MA- co -VAG) and (poly(mPEG 1000 MA- co -VAG), which could self-assemble into micelles and displayed enhanced antitumor activity. The copolymers and the formed micelles were well characterized for their structure, critical aggregation concentration (CAC), morphology, cellular uptake, cell cytotoxicity, and controlled drug release. Cellular uptake and in vitro cytotoxicity assays against human lung cancerous cells (A549) demonstrated that these micelles could be effectively internalized and induced cell apoptosis. These micelles efficiently inhibited tumor growth when injected intravenously into A549 cell derived xenograft tumor bearing Balb/C nude mice using a dose of 10 mg/kg in terms of reduced tumor volume compared to free gemcitabine. In conclusion, PEGylated micelles could protect gemcitabine from rapid plasma metabolism, provided a sustained release and showed enhanced antitumor activity, thus have the potential to be used as novel anticancer drug delivery vehicle.
研究领域:
药学
·
肿瘤学
·
生物材料
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）