ACS Applied Polymer Materials
·
2019
·
IF 0
Longgang Wang,Linlin Zhu,Matthew T. Bernards,Shengfu Chen,Haotian Sun,Xiaolei Guo,Weili Xue,Yanshuai Cui,Dawei Gao
Zwitterionic materials have been employed to achieve excellent biocompatibility and the well-suppressed nonspecific protein adsorption of nanoparticles. However, a thick and compact zwitterionic layer may prevent the modified nanoparticles from entering tumor cells, resulting in low cellular internalization efficiency. To address this problem, new biocompatible micelles (PPIMYC) with a thin zwitterionic layer were designed and prepared. Zwitterionic generation 2 polypropyleneimine dendrimers (G2 PPI) serve as the hydrophilic external shell, and N-(2-mercaptoethyl)oleamide serves as the hydrophobic internal core. Drug-loaded dendritic micelles (PPIMYC-DOX-Ce6) were also prepared by self-assembly of PPIMYC with doxorubicin (DOX) and chlorin e6 (Ce6) to demonstrate chemo-photodynamic dual therapy. As potential drug delivery systems for antitumor therapy, PPIMYC-DOX-Ce6 exhibited sustained drug release under acidic conditions and high stability in fibrinogen solution. In addition, cytotoxicity studies showed an enhanced efficiency of PPIMYC-DOX-Ce6 in killing HeLa cells as compared to free DOX with or without irradiation (660 nm laser). More importantly, both flow cytometry and fluorescence microscopy results indicated that the cellular uptake efficiency of DOX was significantly enhanced in PPIMYC-DOX-Ce6-treated cells relative to free DOX treated cells. The intracellular internalization of PPIMYC-DOX-Ce6 was more efficient under acidic pH, representing the tumor environment, as compared to normal pH. This results from the pH sensitivity of the zwitterionic layer. Temperature was the only environmental factor affecting the cellular internalization process. It is believed that the enhanced intracellular internalization efficiency is due to the thin zwitterionic layer of PPIMYC-DOX-Ce6. The preparation scheme of zwitterionic micelles would offer a new strategy to design novel antitumor drug delivery systems with enhanced cellular internalization efficiency and high stability in a complex medium.
研究领域:
纳米医学
·
癌症研究
·
药剂学
·
材料科学
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DOI
JOURNAL OF DRUG TARGETING
·
2026
·
IF 4.7
Pingping Zhao,Wenhao Yuan,Yuhong Xu,Caifei Jin,Chu Chu,Yan Yang
The transdermal delivery of poorly water-soluble drugs is limited by low aqueous solubility and the stratum corneum permeability barrier. In this study, curcumin was formulated into self-assembled micelles using Tween 20 and polyethylene glycol 400, which exhibited a particle size of 12.5 nm, a zeta potential of −12.5 mV, and a 170-fold increase in solubility. The curcumin micelles (CM) were combined with constant-current iontophoresis (0.45 mA/cm2), to investigate the synergistic enhancement effects and underlying mechanisms. The results showed a 44.2-fold increase in cumulative release over 60 min, with a linear flux–current density relationship (R2 = 0.99). CM exhibited electro-responsive release with an approximate 20-min lag. Under a fixed 2 h total stimulation, pulsed current (4 pulses) nearly doubled the 8-h cumulative release compared to continuous current. Furthermore, both current density and electrode configuration were shown to influence penetration depth and width. Iontophoresis enabled CM to penetrate rat skin to a depth of 270 μm and increased intradermal retention by 258%. In a rat second-degree burn model, the combination therapy significantly accelerated wound healing via promoting angiogenesis, downregulating inflammatory cytokines, and enhancing collagen deposition.
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DOI
高影响因子
POWDER TECHNOLOGY
·
2018
·
IF 3.23
Chao Qin,Xin Yang,Yubing Wu,Yaqi Lv,Li Zhang,Xiaofei Xin,Lei Yang,Wei He,Xiaopeng Han,Lifang Yin,Chunyong Wu
ABSTRACT A matrix metalloproteinases (MMPs) triggered multifunctional micellar system loading traditional chemotherapeutic agent paclitaxel (PTX) and marimastat (MATT), an inhibition of matrix metalloproteinases, was established to prevent tumor growth and metastasis. The micelles were self-assembled by the conjugate synthesized with an MMPs sensitive peptide as the bridge between PTX and poly(ethylene glycol) (PEG). 4T1 cell line derived from a murine breast tumor was selected as the cell model due to its high metastasis. The cytotoxicity assay and cell apoptosis analysis revealed that the sensitive micelles increased the toxicity and cell apoptosis compared with the insensitive micelles. In addition, this system also exhibited high penetration ability in tumor spheroids and significant invasion inhibition with the method of Transwell invasion assay. In the BALB/c mice bearing 4T1 tumors, this system inhibited the growth of the metastatic tumor and prevented the incidence of lung metastasis with low systemic toxicity. And the expression of MMP-2 and MMP-9, which are important in the process of tumor metastasis, was down-regulated. Generally, the data obtained from the in vitro and in vivo studies confirmed that the codelivery of PTX and MATT by the MMPs sensitive micelles achieved not only significant antitumor effect but also obvious inhibition effect of tumor metastasis, which are the leading cause of cancer deaths. This functional particle system may provide a promising strategy for metastatic breast cancer therapy.
研究领域:
肿瘤学
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药学
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生物医学工程
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DOI
高影响因子
POLYMER BULLETIN
·
2018
·Vol. 76
·期 5
·2215-2231
·
IF 1.589
Yu Lili,Yao Lin,Li Li,Liu Shaojing,Jia Zhengxuan,Wu Di
The cationic photo-responsive polymeric micelles (mPEG-b-p(DEMA-co-MMA-CL)) with light-switchable cross-linker were designed and fabricated by atom transfer radical polymerization and quaternization. These micelles were well dispersed spherical with positive charge. The efficient release of encapsulated contents can be triggered by light irradiation. No significant toxicity was observed of copolymer and its photolysis residues at concentrations up to 250 μg/mL. The antitumor activity of camptothecin (CPT) in micelles demonstrated that light triggered the release of CPT, which dramatically improves the cytotoxicity after UV irradiation.
研究领域:
药学
·
高分子化学
·
纳米技术
·
药物递送系统
·
癌症治疗
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产品关联
DOI
高影响因子
Micro & Nano Letters
·
2018
·Vol. 13
·期 9
·1329-1334
·
IF 0.841
Yukui Zheng,Miao Pan,Chao Lu,Daojun Liu
Polypeptide-based amphiphilic brush copolymers PLL- g -(PBLG- b -PEG) and PLL- g -(PZLL- b -PEG) with a poly(L-lysine) (PLL) backbone and amphiphilic oligo(γ-benzyl-L-glutamate)- b -poly(ethylene glycol) (PBLG- b -PEG) or oligo(ε-benzyloxycarbonyl-L-lysine)- b -poly(ethylene glycol) (PZLL- b -PEG) side chains were synthesised, characterised, and evaluated as unimolecular nanocontainers to encapsulate hydrophobic guest molecules. The structure of these brush polymers was modulated by tuning the length of the PLL, PBLG/PZLL, and PEG segments. The final products were characterised with 1 H nuclear magnetic resonance and gel permeation chromatography. The morphology and aggregation behaviours of brush copolymers were examined by using a transmission electron microscope and dynamic light scattering. It was revealed that these water-soluble brush copolymers resembled unimolecular micelles in an aqueous solution. An encapsulation study was performed using pyrene and oil red O as the model compounds, and the results showed that hydrophobic molecules could be solubilised in these unimolecular micelles with high loading capacities. The synthesised polypeptide-based amphiphilic brush copolymers could serve as promising unimolecular nanocarriers for the delivery of hydrophobic drugs.
研究领域:
生物材料学
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高分子化学
·
药物递送系统
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DOI
高影响因子
ACS Applied Materials & Interfaces
·
2018
·
IF 8.097
Zhanwei Zhou,Chenzi Li,Minghua Zhang,Qingyan Zhang,Chenggen Qian,David Oupicky,Minjie Sun
Hydrophobic modification on polycations were commonly used to improve the stability and transfection efficiency of polyplexes. However, the improved stability often means undesired release of the encapsulated siRNA, limiting the application of cationic micelles for siRNA delivery. The current strategy of preparing bioresponsive micelles based on the cleavage of sensitive linkages between polycation and hydrophobic part was far from sufficient, owing to the siRNA binding of the separated polycations from micelles leading to the incomplete release of siRNA. In this study, we propose a new strategy by the combination of micelles disassembly and separated polycations charge reversal. FPBA (3-fluoro-4-carboxyphenylboronic acid) grafted PEI 1.8 k (polyethylenimine) as the polycations of PEI-FPBA and dopamine (with diol-containing moiety) conjugated with cholesterol as the hydrophobic part (Chol-Dopa). The PFCDM micelles was assembled by PEI-FPBA and Chol-Dopa, based on the FPBA-Dopa conjugation. The prepared PFCDM showed strong siRNA loading ability and superior stability in the presence of PBS or serum. Besides, the PFCDM exhibited excellent ATP sensibility. The intracellular ATP could effectively trigger the disassembly of micelles and charge reversal of PEI-FPBA, resulting in the burst release of siRNA in the cytosol. With the property of extracellular stability and intracellular instability, PFCDM displayed good performance on in vitro and in vivo luciferase silencing on 4T1 cells. It should also be noted that the assembly of low molecular weight PEI was relatively safe to cells compared with 25 k PEI. To sum up, the ATP-fueled assembly and charge reversible micelles gave examples for polyplexes to achieve better stability and on demand cargo release at the same time and shows potential to be used for in vitro and in vivo siRNA transfection.
研究领域:
纳米技术
·
药学
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生物医学工程
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2023
·
IF 5.9
Jiaojiao Chen,Yarong Song,Wenqian Yang,Jianhui Guo,Saihui Zhang,Dong Wan,Yonghui Liu,Jie Pan
Chemotherapy remains the primary treatment for cancer; however, conventional chemotherapeutic drugs have several shortcomings, including poor solubility, lack of targeting, low bioavailability, and high toxicity to healthy tissues. In order to overcome these limitations, drug delivery systems (DDS) have emerged as a promising alternative. In this study, we synthesized TPGS3350-PVGLIG-SS-DOX polymeric micelles that incorporate both extracellular MMP2/9 enzyme response and intracellular reduction response at a nanoscale level. The micelles remained stable throughout the blood circulation and only aggregated at the tumor sites, thanks to the enhanced permeability and retention (EPR) effect. Moreover, the tumor tissue showed a high expression of MMP2/9 enzymes, which resulted in the cleavage of the PVGLIG peptide sequence, ultimately leading to an improved phagocytosis efficiency. Under the action of high intracellular GSH concentration, the disulfide bond was broken and DOX was released to induce tumor cell death. The TPSD&D micelles exhibited good tumor inhibitory activity in vivo and significantly reduced toxic side effects on normal tissues. Our work provides a simple method to assemble tumor-targeted prodrug micelles to improve cancer therapy, which holds potential for clinical applications in antitumor therapy.
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DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2023
·
IF 5.8
Jinyu Liu,Yanhao Zhang,Chao Liu,Yuhao Jiang,Zihao Wang,Xinsong Li
Polypeptides are a highly promising carrier for delivering hydrophobic drugs, due to their excellent biocompatibility , non-toxicity, and non-immunogenicity. Herein, a redox and pH dual-responsive poly(ethylene glycol)-SS-b-polypeptide micelles encapsulated with disulfide bridged paclitaxel-pentadecanoic acid prodrug was developed for cancer chemotherapy . First of all, disulfide bridged paclitaxel-pentadecanoic acid prodrug (PTX-SS-COOH) and poly(ethylene glycol)-SS-b-polylysine-b-polyphenylalanine (mPEG-SS-b-PLys-b-PPhe, ESLP) were synthesized and confirmed via NMR, MS, FT-IR or GPC. After that, PTX-SS-COOH (PSH) embedded mPEG-SS-b-PLys-b-PPhe (ESLP/PSH) micelles were prepared by mixing method based on electrostatic interactions and hydrophobic forces. For comparison, mPEG-b-PLys-b-PPhe (ELP) was mixed with PTX-SS-COOH to generate another kind of micelles (ELP/PSH). The characterization of ESLP/PSH micelles through dynamic light scattering (DLS) and transmission electron microscopy (TEM) revealed a spherical structure with a diameter of approximately 170 nm . It is noteworthy that ESLP/PSH micelles displayed a high drug-loading rate of 22.84%, and excellent stability, which can be attributed to the specific interactions between the prodrug and copolymer . Drug release analysis demonstrated that the micelles exhibited a substantial release of PTX in the presence of GSH at pH 5.0, indicating a pH and redox dual responsiveness. In vivo pharmacokinetic study revealed the ESLP/PSH micelles had increased bioavailability and an extended circulation time. Ultimately, antitumor efficacy and systemic toxicity evaluation in 4 T1 tumor-bearing mice confirmed that ESLP/PSH micelles achieved the highest level of tumor growth inhibition (ca. 83%) and the lowest systemic toxicity in comparison with ELP/PSH micelles and commercialized Taxol®. Taken together, the dual responsive micelles represent a promising PTX formulation with potential clinical application in cancer chemotherapy.
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DOI
PubMed
高影响因子
AAPS PHARMSCITECH
·
2020
·Vol. 21
·期 6
·1-13
·
IF 2.401
Zhang Jisen,Su Meiling,Yin Zongning
Currently, there is no specific treatment for acute lung injury (ALI) in clinical practice. In order to efficiently and accurately treat ALI, the advantages of cationic carriers were combined to accelerate the cell uptake. Polycaprolactone-polyethylene glycol carrier (PCL-PEG-COOH, PPC) with good biocompatibility, polycaprolactone-polyethylmethacrylate cationic carrier (PCL-PDMAEMA, PCD), and polycaprolactone-polyethylene glycol carrier connected with high-affinity targeting peptide (Esbp) targeting inflammatory endothelial cells (PCL-PEG-Esbp, PPE) were used to construct the high-molecular polymer micelles (PCD/PPC/PPE). The particle size of the prepared DEX-loaded micelles was 130 ± 4.41 nm, and the Zeta potential was 28.3 ± 0.76 mV. The CMC value of the prepared polymer micelles was 0.643 μg/mL, and it was not easy to depolymerize in the blood circulation. Only about 40% DXM was released from the drug-loaded polymer micelles after 12 h compared with free DXM, indicating that the micelle material had a certain sustained-release performance in vitro release experiments. The safe concentration range of polymer was determined by biocompatibility test. It was recommended that the concentration of polymer micelles should not exceed 0.40 mg/mL to obtain a good compatibility in organisms. The results of cytotoxicity measurement showed that when the content of PCD increased to 50%, the concentration of blank micelles should not exceed 500 μg/mL and the concentration of DXM-loaded micelles should not be higher than 100 μg/mL. It was proved in the cell uptake experiment that the cation carrier of the micelles accelerated the cell uptake. The targeting ability of the targeted micelle group was higher compared with the non-targeted micelle group ( P < 0.01, **). Meanwhile, the targeting ability of the non-targeted micelle group was higher compared with the free group ( P < 0.001, ***). The targeting ability of the non-targeted micelle group was about 2.30 times and the targeted micelle group was about 3.16 times larger than that of the free group. It was also proved in the in vivo targeting experiments that the targeted micelles had a good targeting ability. The results of in vivo imaging of mice showed that the DXM of the micelle group gathered more in the lungs, and the micelle group had a better targeting ability compared with the free DID group. The order of lung targeting intensity was targeted micelles > non-targeted micelles >> free DID group. The targeting ability of polypeptide Esbp to ALI was confirmed. In conclusion, the prepared PCD/PPC/PPE polymer micelles had obvious in vitro and in vivo targeting ability and good biocompatibility. They could be used as a new targeted delivery system for the treatment of ALI in the future.
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DOI
PubMed
高影响因子
International Journal of Polymeric Materials and Polymeric Biomaterials
·
2015
·
IF 3.568
Qingzhi Guo,Dongdong Guan,Baihua Dong,Fangfang Nan,Youzhong Zhang
Candesartan-g-polyethyleneimine-cis-1,2-cyclohexanedicarboxylic anhydride (CD-g-PEI-HHPA, CPH) polymer-drug conjugates based on charge-conversional delivery, enhanced buffering capacity, amidase-triggered drug release, and combined cancer chemotherapy strategies were successfully synthesized for simultaneous and effective codelivery of CD and paclitaxel (PTX) to treat cervical cancer. The CPH polymer-drug conjugates could self-assemble into core-shell structure micelle of around 100 nm in diameter with negative surface charge and were employed to load PTX to formulate binary drug delivery system. The CPH polymeric micelles could mediate quick endosomal escape and amidase-responsive drug-release manners. In vitro cytotoxicity and in vivo investigations confirmed CPH binary drug delivery system exerted strong antitumor efficacy.
研究领域:
药学
·
肿瘤学
·
药物递送系统
·
聚合物化学
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产品关联
DOI
高影响因子
BIOMACROMOLECULES
·
2015
·
IF 5.75
Haisheng Wang,Wenbo Zhang,Changyou Gao
The amphiphilic pyrene-containing random copolymers with light-responsive pyrene ester bonds were synthesized by copolymerizing 1-pyrenemethyl acrylate (PA) and N,N-dimethylacrylamide (DMA). The P(DMA-co-PA) copolymers formed spherical micelles in water, which were transformed into nanorods as a result of cleavage of the pyrene ester bonds under UV irradiation. In vitro culture with A549 cells and Raw cells showed that compared to the nonphotodegradable ones, the photodegradable P(DMA-co-PA) micelles caused significantly higher cytotoxicity under the same UV irradiation. The intracellular reactive oxygen species (ROS) level had a positive correlation with the cytotoxicity regardless of the cell types. The nonphotodegradable pyrene-containing micelles produced a lower level of ROS under UV irradiation. However, the photodecomposable P(DMA-co-PA) micelles produced a significant higher level of ROS under the same trigger of UV irradiation, which caused the shape transformation of micelles to nanorods and higher cytotoxicity simultaneously.
研究领域:
高分子化学
·
生物医学工程
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF SURFACTANTS AND DETERGENTS
·
2015
·Vol. 18
·期 5
·739-746
·
IF 1.685
Zhihu Yan,Caili Dai,Mingwei Zhao,Guang Zhao,Yuyang Li,Xuepeng Wu,Yifei Liu,Mingyong Du
A noncovalent bonding method was utilized for forming multiresponsive surface-active ionic liquids in mixed N -alkyl- N -methylpiperidinium bromide (C 16 MDB) and potassium phthalic acid (PPA). Rheology, cryogenic-transmission electron microscopy, dynamic light scattering and nuclear magnetic resonance were used to investigate the aggregation property of surface-active ionic liquids in aqueous solution. The efficiency of the shielding effect in the form of hydrophobic effects and electrostatic attraction between PPA and the C 16 MDB headgroup under diverse pH conditions is found to be the root cause of a shift in the aggregate's morphological transformation. In addition, the molecular motion of surfactant molecules becomes more active as the temperature increase provides the property of thermoresponsive to the surface-active ionic liquid system.
研究领域:
化学
·
材料科学
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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）