Materials Science & Engineering C-Materials for Biological Applications
·
2018
·
IF 5.08
Xiang Feng,Yunfeng Zhou,Xin Xie,Ming Li,Hao Huang,Liangliang Wang,Xiao Xu,Jingmou Yu
In this study, prostate-specific membrane antigen (PSMA)-targeted and core-crosslinked micelles were developed based on prostate cancer-binding peptide (PCP) modified glycol chitosan-lipoic acid (PGC-LA) conjugate. The degree of substitution was 5.2 PCP groups and 10.7 lipoic acid groups per 100 sugar residues of glycol chitosan in PGC-LA copolymer. Docetaxel (DTX) was chosen as a model anti-tumor drug. The DTX-loaded micelles were prepared by an o/w method, and core-crosslinked micelles were further constructed by using a catalytic amount of dithiothreitol. The mean diameter of DTX-loaded core-crosslinked PGC-LA (DTX-PGC-LA/cc) micelles was 397 nm determined by dynamic light scattering (DLS). In vitro DTX released from core-crosslinked micelles was slower than that from non-crosslinked counterpart. Blank micelles exhibited good biocompatibility. Additionally, cellular uptake and cytotoxcity of PCP-modified micelles were higher than those of micelles without PCP in PSMA-positive LNCaP cells. Importantly, DTX-PGC-LA/cc demonstrated the stronger anti-tumor efficacy against LNCaP tumor xenograft models than DTX injection and other DTX-loaded micelles. Taken together, this study provides a potential way in developing actively targeted and core-crosslinked micelles for hydrophobic drug delivery in cancer therapy.
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PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2020
·
IF 7.727
Cheng Hu,Fanjun Zhang,Linyu Long,Qunshou Kong,Rifang Luo,Yunbing Wang
Disease microenvironment stimuli-responsive hydrogels are of special interests in enhancing the drug delivery specificity for biomedical applications. In order to achieve specific drug release characteristic at the inflammation region, a smart pH- and reactive oxygen species (ROS)-responsive injectable hydrogel with self-healing and remodeling capability was designed in our present work. By grafting phenylboronic acid to the side chain of the alginate polymer, a highly specific dual-responsive hydrogel with low pH and high ROS was obtained. Moreover, the hydrogel was endowed with antibacterial and anti-inflammatory properties respectively via the effective assembly of antibiotic amikacin (AM), and anti-inflammatory drug naproxen (Nap) which were preloaded into the micelles . Such hydrogel formulation not only preserved the structural integrity and excellent rheological properties of the hydrogel but also allowed for a controllable drug release rate at inflammation sites. The antibacterial experiment results in vitro demonstrated that the hydrogel could effectively kill bacteria by amikacin release, with the inhibitive rate reached to 90% for S. aureus and 98% for P.aeruginosa . Furthermore, the anti-inflammatory drug naproxen was also controllably released from the ROS-responsive micelles within 24 h under pH 5.0, and 10 mM H 2 O 2 in vitro . Most importantly, the smart hydrogels showed good biocompatibility , and greatly promoted the healing of infected wounds in vitro by cell scratch assay. In addition, it efficiently reduced the levels of TNF-α (the pro-inflammatory cytokine) by 2.80 times, and increased IL-10 (anti-inflammatory cytokine) by 2.41 times than the hydrogel control without antibiotic and anti-inflammatory drug. Within the dual-responsiveness of pH and ROS, the hydrogel reduced the inflammation response of the surrounding tissues significantly and accelerated the healing process of the infected area. Collectively, this smart hydrogel formula containing antibiotic and drug-loaded micelles is very promising to be applied topically against various microbial infections. We believe that this strategy can also be applied to various disease treatments.
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PubMed
高影响因子
POLYMER BULLETIN
·
2012
·Vol. 69
·期 5
·597-620
·
IF 1.532
Luo Yan-Ling,Yu Wei,Xu Feng
pH-sensitive hydrophilic poly(methacrylic acid)- b -poly(ethylene glycol)- b -poly(methacrylic acid) (PMAA- b -PEG- b -PMAA) triblock copolymers were synthesized through atom transfer radical polymerization, and were characterized by FT-IR, 1 H NMR, and GPC. The as-synthesized polymers can self-assemble into stable and almost spherical nanomicelles in aqueous solution with an average size range from 18 to 89 nm, depending on the micellar concentrations, while they assumed well-defined spherical morphologies in PBS solutions. The micellization behavior in different media was investigated by a fluorescence spectroscopy technique, UV–Vis transmittance, and dynamic light scattering measurements. The critical micelle concentration and size of the micelles decrease with the increasing the length or molecular weights of PEG and PMAA chains. A pH-dependent phase transition behavior produces at a pH value of about 5.2, and the stable pH micellization behavior varied within a narrow pH range from ca. 4.8 to 7.4. These triblock copolymers are generally low cytotoxicity at a micellar concentration below 400 mg L −1 , as revealed by the MTT assay. The prednisone release and release kinetics studies disclosed that these pH-sensitive polymeric micelles are good carriers for the drug delivery.
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高影响因子
Drug Delivery and Translational Research
·
2018
·Vol. 8
·期 5
·1090-1102
·
IF 3.395
Xie Yonghui,Liu Chenchen,Huang Hongwei,Huang Jian,Deng Aiping,Zou Ping,Tan Xueying
This study aimed to investigate the improved therapeutic efficacy and pharmacokinetic profiles of simvastatin (SIM) with imparted bone targeting potential using tetracycline-mediated PEG-PLGA (TC-PEG-PLGA) micelles in osteoporotic rats. The SIM-loaded TC-PEG-PLGA (TC-PEG-PLGA/SIM) micelles were evaluated for particle size, morphology, stability, loading efficiency, cell viability, bone mineral binding ability in vitro, mineralization, pharmacokinetics, and pharmacodynamics. TC-PEG-PLGA conjugates were successfully and could self-assembly form micelles in aqueous medium with a 19.4 μg/mL critical micelle concentration. Then, TC-PEG-PLGA/SIM micelles were prepared with solvent diffusion method, and the obtained micelles (56.21 ± 7.39 nm average size; 81.8 ± 3.1% encapsulation efficiency; and 7.56 ± 0.27% drug loading) led to the prolonged release of SIM from micelles. Cellular uptake test indicated that TC had no effects on micellar internalization and micellar internalization was mainly involved with clathrin-mediated endocytic pathway. In vivo pharmacokinetic results indicated that TC-PEG-PLGA/SIM micelles exhibited a significantly prolonged time in systemic circulation and were preferentially accumulated in bone tissue. TC-PEG-PLGA/SIM micelles showed better therapeutic effects, as reflected by the improved bone mineral density, bone mineral content, and bone mechanical strength. Overall, these results suggested that TC-PEG-PLGA/SIM micelles provide several advantages, including prolonged systemic circulation, enhanced bone tissue distribution, and improved therapeutic outcomes in osteoporotic rats.
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高影响因子
Polymer Chemistry
·
2014
·Vol. 5
·期 14
·4348-4357
·
IF 5.368
Qiangfang He,Jianbing Huang,Hui Liang,Jiang Lu
A well-defined block copolymer polystyrene-block-poly(2-hydroxy-5-vinylbenzaldehyde) (PS-b-PHVB) was synthesized by reversible addition–fragmentation chain transfer (RAFT) polymerization of HVB using a trithiocarbonate terminated polystyrene macro-chain transfer agent. Sequential grafting of monoamine-terminated PEG (PEG–NH2) and 2-(2-aminoethoxy)ethanol (AME) onto the HVB blocks of PS-b-PHVB via aldehyde–amine condensation afforded an amphiphilic block copolymer PS-b-(PHVB-g-PEG-and-AME) bearing a pendant salicylidene Schiff base with a precise structure. PS-b-(PHVB-g-PEG-and-AME) could self-assemble in ethanol into micelles with salicylidene Schiff base groups at the core–shell interface. Addition of Zn2+ ions into the resulting micellar solution not only endowed the micelles with fluorescent features but also enabled the resulting luminescent micelles to be stabilized through ionic cross-linking in consequence of the salicylaldimine–Zn2+ complexation. The obtained fluorescent cross-linked micelle was “light-controllable” in terms of its fluorescence emission and cross-linking structure due to the reversibility of the salicylaldimine–Zn2+ coordinative bond in response to light stimuli. The reversible fluorescence decrease and recovery could be achieved periodically upon alternative 254 nm UV irradiation and maintaining in the dark, and the micelles could be de-stabilized by UV irradiation-induced de-cross-linking. The capture of guest molecules and the light-triggered release of the guests for this Zn2+ coordinated micelle were also demonstrated using the coumarin-153 dye as a model guest molecule.
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高影响因子
AAPS PHARMSCITECH
·
2018
·Vol. 19
·期 5
·2395-2406
·
IF 2.666
Xiao Yu,Wang Shuang,Zong Qingyu,Yin Zongning
Single chemotherapeutic agent like paclitaxel (PTX) has shown some limitations in anti-tumor treatment, such as undesirable side effects, multidrug resistance, and high toxicity. In order to reduce the toxicity of PTX and increase the anti-tumor effect, folate-modified amphiphilic and biodegradable biomaterial was developed to co-deliver PTX and metformin (MET) for exerting the synergistic effect. PTX was physically entrapped in the hydrophobic inner core of the amphiphilic block copolymer by a solvent evaporation method, whereas MET was chemically conjugated to the hydrophilic terminals of copolymer via a pH-sensitive cis -aconityl linkage (Cis). The in vitro release behaviors of the drugs were analyzed by high-performance liquid chromatography (HPLC), and the synergistic effect of the drugs was evaluated by a Q value method. Results showed that drug-loaded micelles with an average size about 100 nm were successfully constructed. In acidic environments, the chemically conjugated MET was rapidly released after the breakage of sensitive bond between drug and copolymer. In vitro anti-tumor studies demonstrated that MET and PTX had a synergistic effect and co-delivery micelles induced higher cytotoxicity and apoptosis against 4T1 breast cancer cells than free drugs. Furthermore, folate-targeted co-delivery micelles increased the cellular uptake of drugs and were found to be effective for the treatment of solid tumor in vivo . These findings indicated that co-delivery of MET and PTX through the polymeric micelles is a promising strategy for cancer therapy.
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高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Ling Wang,Jie Li,Danya Zhang,Songwei Tan,Guiying Jiang,Xueqian Wang,Fei Li,Ying Zhou,Pingbo Chen,Rui Wei,Ling Xi
Metastasis and recurrence are the main causes of failure in the treatment of ovarian cancer (OC). Immunotherapy has brought new opportunities for cancer treatment, but the presence of the immunosuppressive tumor microenvironment limits its application in OC. Here, we prepared a kind of intelligent nanomicelles that could inhibit OC metastasis and recurrence by combining photothermal tumor ablation and immune remodeling. In this study, Indocyanine green (ICG), a photosensitizer and Monophosphoryl lipid A (MPLA), a Toll-like receptor 4 agonist, were encapsulated into the core of PEG-PLGA nanocarrier, and the surface was further modified with tumor-targeting peptide TMTP1. The formed TP1-IM nanomicelles with enhanced tumor accumulation could enable robust photothermal ablation of the primary tumor, and induce immunogenic cell death, release tumor-associated antigens, and DAMPs to form an endogenous in situ tumor vaccine by a single intravenous injection, which could effectively inhibit the growth of OC. Moreover, PTT with TP1-IM nanomicelles in combination with programmed cell death ligand 1 (PD-L1) checkpoint blockade could induce strong anti-tumor immune responses, relieve the immunosuppressive tumor microenvironment, and thus effectively inhibit the metastasis of OC. In addition, the combination strategy could produce long-term immune memory effects in treated mice to prevent the recurrence of tumors. Our work provides a new and individualized strategy for the treatment of OC and is expected for clinical transformation in the future for most components are clinically approved.
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产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2021
·
IF 5.89
Yu Juan,Xu Chaoqun,Lu Chuanwei,Liu Qian,Wang Jifu,Chu Fuxiang
Preparation and application of sustainable polymers derived from renewable resources are of great significance. The aim of this study is to synthesize a kind of sustainable polymeric micelles from rosin and vegetable oils via atom transfer radical polymerization (ATRP) and to investigate the doxorubicin delivery properties of these micelles. Dehydroabietic acid–based poly lauryl methacrylate (DA-PLMA) with narrow PDI of 1.13 was prepared in a well-controlled process using rosin as an ATRP initiator. Thereafter, carboxylic groups were introduced to form poly methacrylic acid (PMAA) moieties in DA-PLMA polymer via acid hydrolysis. The resulted DA-PLMA-PMAA could self-assemble in water to form pH-dependent polymeric micelles with a diameter of ∼65 nm and PDI as low as 0.105. Owing to the existence of rosin, DA-PLMA-PMAA micelles also showed self-fluorescence properties. In addition, Dox-loaded micelles were prepared in aqueous solution with the drug-loading capacity as high as 16.0% and showed sustained-release characteristics. These results demonstrate great promise for designing polymeric micellar from rosin and vegetable oils.
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高影响因子
FOOD CHEMISTRY
·
2013
·
IF 3.334
Wenjian Li,Hailong Peng,Fangjian Ning,Lihua Yao,Mei Luo,Qiang Zhao,Xuemei Zhu,Hua Xiong
Novel amphiphilic chitosan derivative of N , N -dimethylhexadecyl carboxymethyl chitosan (DCMCs) was synthesised. The physical properties of DCMCs were characterised by Fourier transform-infrared spectroscopy, nuclear magnetic resonance spectroscopy, X-ray diffraction and differential scanning calorimetry. DCMCs can form core–shell micelles with low critical micelle concentration (31 mg L −1 ). The core–shell micelles exhibited spherical shape with positive charge (+50.7 mV) and narrow size distribution (polydispersity index <0.5). Vitamin D 3 (VD 3 ) was initially used to load into the core–shell micelles, and the solubility of VD 3 was improved with higher encapsulation efficiency (53.2%). The in vitro release processes of VD 3 from the core–shell micelles were initially rapid and then followed by a sustained release. The Higuchi model was the most suitable for describing the entire release procedure. DCMCs core–shell micelles are promising carriers for VD 3 and other hydrophobic bioactive food factors.
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高影响因子
POLYMER
·
2015
·
IF 3.562
Lin Wang,Yin Wang,Qiao Jin,Fan Jia,Haibo Wang,Jian Ji
Biomimic hyaluronic acid (HA) prodrug micelles with pH and reduction responsiveness were prepared by chemical graft of phosphorylcholine and doxorubicin (DOX) to the backbone of HA. DOX was conjugated to HA by pH-sensitive hydrazone bonds which could be hydrolyzed under acidic conditions and thus resulted in controlled release of DOX. Besides, the HA prodrug micelles were cross-linked via reduction-responsive disulfide bonds to improve the stability of the micelles. The HA prodrug can form remarkable core–shell micelles with a quite narrow size distribution which was confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The in vitro drug release studies showed that there was a dramatic release under endosome pH (pH = 5.0) and reductive environment (10 mM of dithiothreitol) than that at normal physiological environment (pH = 7.4). Greater uptake of DOX from HA prodrug micelles was observed in the CD44 receptor highly expressed MDA-MB-231 cell line, compared to the results from the CD44-negative cell line, NIH3T3, which was demonstrated by the flow cytometry and fluorescence microscopy . The glutathione (GSH)-responsive behaviors were studied as well. The micelles showed higher cellular proliferation inhibition against glutathione monoester (GSH-OEt) pretreated MDA-MB-231 cells than that of the non-pretreated and buthionine sulfoximine (BSO) pretreated ones. These results suggested that such pH/reduction dual-responsive prodrug micelles may enhance the selective inhibition to cancer cells which exhibit higher levels of GSH concentration and provide favorable platforms for cancer therapy.
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高影响因子
JOURNAL OF BIOMATERIALS APPLICATIONS
·
2019
·
IF 2.442
Yan Zheng,Shudan Shi,Yaru Liu,Yandan Zhao,Yuqi Sun
Liver cancer is one of the most common malignant tumors. Chemotherapy drugs have been widely used in the anti-hepatoma research. However, low targeting efficiency and serious adverse reaction are their main drawbacks. Liver tumor was proved to have a slightly acidic microenvironment (pH 4.5–5.5) and many glycyrrhetinic-acid-specific binding sites. Therefore, in the present study, the glycyrrhetinic acid- and hydrazone bond-modified micelles were designed. mPEG-HZ-PLA and GA-PEG-PLA copolymer were synthesized to prepare glycyrrhetinic-acid-modified pH-sensitive polymeric micelles (GA-PEG-HZ-PLA). The targeted pharmacokinetics was used to evaluate the effect in hepatoma 22 tumor-bearing mice after the micelles were administered intravenously. The contents of coumarin-6 in blood and tissues were determined through high-performance liquid chromatography using a fluorescence detection (HPLC-FLD) with coumarin-30 as inner standard. The micelles have shown long-circulation effects and two-department models. In the targeting pharmacokinetics, the relative intake efficiency, targeted efficiency, relative targeting efficiency, and concentration ratio of GA-PEG-HZ-PLA in the tumor were 3.24, 4.04, 3.00, and 2.47, respectively. We have demonstrated that GA-PEG-HZ-PLA was more effectively accumulated in the liver and tumor. Thus, the prepared active-targeted and pH-sensitive micelles modified with glycyrrhetinic acid structure and hydrazone bond are promising tools for effective liver cancer therapy.
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高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2022
·
IF 5.062
Junxu Hao,Jinglei Wang,Hao Pan,Yuli Sang,Dazhuang Wang,Zeyu Wang,Jiao Ai,Bin Lin,Lijiang Chen
In this study, the ideal polymer materials were selected by molecular dynamics (MD) and dissipative particle dynamics (DPD) simulation methods, and pH and redox-sensitive micelles were prepared according to the simulation results. Through experiments, we successfully prepared hydrophilic block polyethylene glycol monomethyl ether (mPEG) connected hydrophobic block polylactic acid-glycolic acid (PLGA) amphiphilic polymer, and connected with redox fragment containing disulfide bond , and then connected with amide bond doxorubicin (DOX) to form mPEG-PLGA-SS-DOX prodrug , and further physical embedded free DOX. Finally, we obtained a particle size of 47.04 ± 0.103 nm, the potential of −23.8 ± 0.189 mV, Polymer dispersity index (PDI) of 0.231 ± 0.001, transmission electron microscopy (TEM) showed that it was spherical mPEG-PLGA-SS-DOX/DOX nanoparticles , its entrapment efficiency (EE) was 68.2%, loading content was 16.72%. The cumulative release of mPEG-PLGA-SS-DOX/DOX was 87.39% in a pH 5.0 and 10 mM Glutathione (GSH) tumor simulation environment. It was less toxic to normal cell HEK293 and more cytotoxic to HepG2 tumor cells. It showed that it was an excellent anti-tumor nano-drug. In addition, the application of computer simulation in the design of nanomedicine also provided a new research idea for the research of nanomedicine .
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