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Journal of Biomedical Nanotechnology · 2015 ·Vol. 11 ·期 3 ·428-435 · IF 5.338

Controlled Dual Drug Release and In Vitro Cytotoxicity of Electrospun Poly(lactic-co-glycolic acid) Nanofibers Encapsulated with Micelles

Liu Wanyun,Wei Junchao,Wei Yen,Chen Yiwang

In order to realize controlled dual release of two hydrophobic drugs with distinct rates in a vehicle, novel poly(lacticco-glycolic acid) (PLGA) composite nanofibers encapsulated with micelles were successfully fabricated by “emulsionelectrospinning.” Brefeldin A (BFA) was firstly embedded in monomethoxy-poly(ethylene glycol)-b-poly(L-lactide) (MePEGPLLA) micelles. By means of “emulsion-electrospinning,” paclitaxel (PTX) and polymeric micelles contained BFA were successfully loaded into the electrospun PLGA composite nanofibers. The in vitro release results demonstrated that the location of the drugs in the electrospun fibers determined their release profiles. BFA had a long-term and sustained release while PTX had a relatively rapid release in the dual drugs delivery system. In vitro cytotoxicity studies revealed that the composite nanofibers with two drugs restrained HepG-2 cells more efficiently. These results strongly suggested that the electrospun composite nanofibers containing polymeric micelles can be used as an effective controlled dual release of hydrophobic drugs and were suitable for postoperative chemotherapy of cancers.

✓ 已验证 DOI PubMed 高影响因子
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MACROMOLECULES · 2023 · IF 5.5

Unraveling Chain Exchange Kinetics in Mixed Micelles through FRET: Impact of Segment Interactions between Hydrophilic Polymers in the Corona

Anhong Liu,Xiaodong Ye

Mixed micelle systems have gained significant attention due to their ability to integrate multifunctionality based on different copolymers. However, an understanding of chain exchange behavior in mixed micelles is limited. In this study, we reported a mixed micelle system where noncovalent cross-linking between the corona blocks enhanced micelle stability. Specifically, we utilized polystyrene-block-poly(2-ethyl-2-oxazoline) (PS-b-PEtOx) and polystyrene-block-poly(methacrylic acid) (PS-b-PMAA) to form the mixed micelle system. Donor- and acceptor-labeled PS-b-PEtOx was employed to investigate the chain exchange kinetics using fluorescence resonance energy transfer (FRET). The addition of PS-b-PMAA facilitated the formation of hydrogen bonds between EtOx and protonated MAA units, resulting in a noncovalent cross-linked corona. As the pH decreases, the percentage of affected PS-b-PEtOx gradually increases, while the extra energy barrier first decreases and then increases. This is mainly due to the conformational changes of PMAA chains, which cause crowding between the core and shell, and the interactions between PMAA and PEtOx, especially hydrogen bonding. This study demonstrates that the hydrogen-bonded cross-linking of the corona in the mixed micelle system can effectively control the chain exchange rate and improve micelle stability.

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Theranostics · 2016 · IF 8.854

Versatile pH-response Micelles with High Cell-Penetrating Helical Diblock Copolymers for Photoacoustic Imaging Guided Synergistic Chemo-Photothermal Therapy

Shengyu Shi,Yajing Liu,Yu Chen,Zhihuang Zhang,Yunsheng Ding,Zongquan Wu,Jun Yin,Liming Nie

With high optical absorption efficiency, near infrared (NIR) dyes have been proposed as theranostic agents for fluorescence imaging, photoacoustic imaging (PAI), and photothermal therapy (PTT). However, inherent hydrophobicity and short circulation time of small molecule hinder the further biomedical application. Herein smart amphiphilic copolymer was synthesized containing IR780/camptothecin@poly(ε-caprolactone) (IR780/CPT@PCL) as core, helical poly(phenyl isocyanide) (PPI) blocks as shell with the pH-responsive rhodamine B (RhB) moieties in the core-shell interface. With hydrophilic helical PPI coronas, these micelles present significantly enhanced cell-penetrating capacity that plays a key role in facilitating intracellular delivery of various cargos. By encapsulating CPT and IR780 molecules, the multifunctional self-assemble probe has huge potential to realize functional cooperativity and adaptability for cancer diagnosis and therapy. The in vitro and in vivo experimental results demonstrate that the pH-triggered fluorescent responsiveness and strong acoustic generation permit them efficient fluorescent and PA signal sensing for cancer diagnosis. Moreover, with 808 nm laser irradiation, the generated heat significantly improves the drug release from PCL core, leading to synergetic chemo-photothermal therapy and decreases tumor recurrence rates in mice. Overall, the biocompatible multifunctional micelles with these combined advantages can potentially be utilized for PAI guided disease diagnosis and tumor ablation.

✓ 已验证 DOI PubMed 高影响因子
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MACROMOLECULAR BIOSCIENCE · 2015 ·Vol. 15 ·期 10 ·1411-1422 · IF 3.851

pH-Responsive H-Type PMAA2-b-HTPBN-b-PMAA2 Four-Arm Star Block Copolymer Micelles for PTX Drug Release

Yan-Ling Luo,Mei Han,Feng Xu,Ya-Shao Chen,Yong-Qin Zhang

pH-Responsive H-type poly(methylacrylic acid- block -four hydroxyl terminated poly(butadiene-acrylobitrile)- block -poly(methylacrylic acid (PMAA 2 - b -HTPBN- b -PMAA 2 ) block copolymers were synthesized via atom transfer radical polymerization and the follow-up hydrolysis, and characterized by 1 H NMR, FT-IR and SEC . The block copolymers could self-assemble into nanoscale spherical core-shell micelle aggregates in aqueous solution, and the physicochemical properties depended on the system composition and pH media, with pH phase transition at 5.7–6.1. The copolymer micelle aggregates exhibited pH-triggered drug release and cytotoxicity, and could potentially be used as drug targeting release carriers.

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Small · 2016 ·Vol. 12 ·期 23 ·3155-3163 · IF 8.315

Quantitative Control of Pore Size of Mesoporous Carbon Nanospheres through the Self-Assembly of Diblock Copolymer Micelles in Solution

Hao Tian,Zhixing Lin,Fugui Xu,Jingxu Zheng,Xiaodong Zhuang,Yiyong Mai,Xinliang Feng

This paper reports facile synthesis of nitrogen-doped mesoporous carbon nanospheres (MCNSs) with average diameters of around 300 nm and well-controlled pore sizes ranging from 8 to 38 nm, by employing polystyrene- b -poly(ethylene oxide) (PS- b -PEO) diblocks with different PS block lengths as the soft templates and dopamine as the carbon-rich precursor. For the first time, a linear equation is achieved for the quantitative control of the average pore size of MCNSs by simply adjusting a block length of diblock copolymer. The resultant MCNSs possess high surface areas of up to 450 m 2 g −1 and nitrogen doping contents of up to ≈3 wt%. As electrode materials of supercapacitors, the MCNSs exhibit excellent electrochemical performance with high specific capacitances of up to 350 F g −1 at 0.1 A g −1 , superior rate capability, and cycling stability. Interestingly, the specific capacitance of the MCNSs reduces linearly with increasing pore size, whereas the normalized capacitance by specific surface area remains invariable. This represents a new spectrum of the relationship between electrochemical capacitance and pore size (>5 nm) for porous carbons, which makes a complement to the existing spectra focusing on pore diameters of <5 nm.

✓ 已验证 DOI 高影响因子
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Journal of Materials Chemistry A · 2014 ·Vol. 2 ·期 35 ·14481-14492 · IF 0

Dispersion of carbon nanotubes in water by self-assembled micelles of branched amphiphilic multifunctional copolymers with photosensitivity and electroactivity

Ren Liu,Xuebiao Zeng,Jingcheng Liu,Yuanyi Zheng,Jing Luo,Xiaoya Liu

Noncovalent surface modification has been proved to be one of the effective strategies for enhancing the properties of multi-walled carbon nanotubes (MWCNTs). When a non-covalent modification method is appropriately designed, novel opportunities for better performance of CNTs can be expected. In this paper, a novel kind of branched amphiphilic photo-sensitive and electro-active copolymer (BP(VCz/VM-alt-MA); BPVCM) was synthesized through a simple one-pot free radical copolymerization with 7-(4-vinylbenzyloxy)-4-methyl coumarin (VM), maleic anhydride (MA), 4-vinylbenzyl thiol (VBT) and 9-(4-vinylbenzyl)-9H-carbazole (VCz) as monomers. The copolymer BPVCM can self-assemble into homogeneous spherical micelles along the side-walls of MWCNTs and efficiently disperse MWCNTs in aqueous solution. In addition, the photosensitive coumarin groups of the copolymer chain undergo crosslinking under UV-irradiation, which leads to the encapsulation of MWCNTs in the crosslinked micelles and greatly improves the stability of the obtained MWCNT suspension. More interestingly, the electroactive carbazole moieties of the BPVCM–MWCNT composites could polymerize via an electrochemical polymerization method and form a MWCNT based conducting coating on the modified glassy carbon electrode (GCE), which eventually increases the number of electroactive sites and significantly accelerates the electron transfer. This novel preparation method permits us to obtain carbon nanotube hybrids exhibiting high water-dispersibility and stability while preserving their outstanding electrical properties, and would be valuable for construction of microelectronics and electrochemical sensors.

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Materials Chemistry Frontiers · 2019 ·Vol. 3 ·期 4 ·606-614 · IF 0

Self-assembly of positively charged polymer patchy micelles in organic solutions and the reversible ultrasound responsivity of the assemblies

Ya Zhao,Weijing Fan,Hanying Zhao

Self-assembly of asymmetric structures has been attractive for applications in the fabrication of hierarchical structures. However, the role of the electrostatic interaction in the self-assembly of charged asymmetric particles in organic solvents has not been fully understood. In this research, self-assembly of positively charged patchy micelles in organic solutions and the reversible ultrasound responsivity of the assemblies are studied. Surface micelles (s-micelles) with cross-linked/quaternized poly(2-(dimethylamino)ethyl methacrylate) (q-PDMAEMA) cores and poly(oligo(ethylene glycol) monomethyl ether methacrylate) (POEGMA) coronae were prepared on the surfaces of silica particles. Positively charged patchy micelles were synthesized upon cleavage of the s-micelles. In THF, the patchy micelles self-assemble into vesicles with positively charged q-PDMAEMA in the walls and POEGMA in the coronae. The average size of the vesicles is dependent on POEGMA chain length. The repelling electrostatic interaction between the positively charged q-PDMAEMA patches in the walls is unfavorable for the achievement of low free energy of the assemblies, but it is energetically favorable for the vesicles to overcome energy barriers in the dissociation of the structures under ultrasound irradiation. The vesicle structures present reversible ultrasound responsivity. Under sonication the vesicles formed by patchy micelles dissociate into transient nanostructures, including aggregates and isolated patchy micelles. When the ultrasound is switched off, the transient nanostructures self-assemble into vesicles. By contrast, crosslinked vesicles do not show ultrasound responsivity. This research provides a new approach to the fabrication of responsive assemblies based on asymmetric structures, and the assemblies could find potential applications in medicine and bioengineering.

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ACS Applied Materials & Interfaces · 2025 · IF 8.2

Aggregation-Induced Emission-Active Toroidal Micelles from a Conjugated Polymer: A Selective Phototheranostic Nanoplatform for Targeting Gram-Positive Bacteria

Ziyu Yue,Sameer Hussain,Yining Feng,Chunhong Zhu,Cibin Zhao,Chunqiang Liu,Xueyi Liu,Yi Hao,Pengchen Ma,Ruixia Gao

Developing advanced antimicrobial photosensitizers that target bacteria precisely is highly desirable but challenging. Traditional photosensitizers demonstrate reduced reactive oxygen species (ROS) production and quenched fluorescence upon aggregation in water, significantly affecting their phototheranostic performance. In this study, water-dispersible toroidal micelles (TPE-BT Mic) with excellent fluorescence properties and ROS generation are prepared by using aggregation-induced emission (AIE)-active conjugated polymer TPE-BT as the photosensitizer and vancomycin-decorated Pluronic F127 as both the encapsulating and targeting material. The stable toroidal micelles not only promote the aggregation of TPE-BT and induce an AIE effect but also improve its water dispersibility and biocompatibility. TPE-BT Mic with vancomycin targeting groups selectively bind to Gram-positive bacteria Staphylococcus aureus (S. aureus) via the d-alanyl-d-alanine terminus of peptidoglycan, showing strong bioimaging performance. They achieved over 97% killing efficiency for S. aureus with low white-light irradiation (20 mW/cm2). Thus, TPE-BT Mic are promising for treating Gram-positive bacterial infections and offer an innovative approach for creating effective photosensitizers to combat the menace of drug resistance.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2025 · IF 8.5

Environmental responsive dual-drug synergistic and dual-targeted polymer micelles based on chondroitin sulfate for treatment of breast cancer

Litao Hu,Huiling Ma,Chunpeng Yang,Kang Wang,Xu Ji,Tingxue Xu,Hong Xu,Yinan Zhao,Yuhong Zhen

Targeted drug delivery strategy can accurately deliver multiple drugs to tumor cells by biocompatible materials, enhance the therapeutic effect and weaken adverse side effects. Chondroitin sulfate (CS) is a biodegradable material which has dual-targeting ability to CD44 receptors and Golgi apparatus. Flurbiprofen is a COX-2 inhibitor that can be used as an anticancer adjuvant in combination with docetaxel to enhance the antitumor effect. Herein, docetaxel and flurbiprofen were coupled to CS via disulfide bond and ester bond respectively to prepare polymer conjugates chondroitin sulfate-docetaxel (C-ss-D) and chondroitin sulfate-flurbiprofen (C-F). Then the reduction-sensitive micelles C-ss-D and the pH-sensitive micelles C-F were constructed by self-assembly respectively, and the dual-drug micelles C-F/C-ss-D were further prepared. C-F/C-ss-D displayed uniform spherical shape, negative surface charge, and achieved controlled drug release in slightly acidic and reductive tumor microenvironment. C-F/C-ss-D exhibited remarkable targeting ability towards tumor cells and Golgi apparatus, demonstrated potent cytotoxic effect on MCF-7 cells, and induced apoptosis by regulating the expression of COX-2 and apoptosis-related proteins. C-F/C-ss-D effectively inhibited tumor growth in MCF-7 xenograft mice with low toxicity to blood and major organs. Therefore, the environmental responsive dual-drug synergistic and dual-targeted micelles based on CS have great potential for the treatment of breast cancer.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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BIOMATERIALS · 2021 · IF 12.479

Construction and evaluation of novel αvβ3 integrin ligand-conjugated ultrasmall star polymer micelles targeted glomerular podocytes through GFB permeation

Chengyuan Huang,Xuan Zhao,Meiling Su,Zongning Yin

As glomerular cells, podocytes are the last line of defense for glomerular filtration barriers (GFB) and play a critical role in chronic kidney disease (CKD). Podocyte-targeted drug delivery is a promising direction in the treatment of CKD. In this study, we constructed four-arm star polymers conjugated with a novel linear RWrNM peptide. And poly ε-caprolactone (PCL) hydrophobic core and brush poly (2-hydroxyethyl methacrylate) (PHEMA) hydrophilic shell were synthesized by ROP and SET LRP polymerization. The PHEMA modified by succinic anhydride was coupled with the novel linear RWrNM peptide, and then the PCL hydrophobic core was loaded with dexamethasone acetate (Dexac) to form micelles with stable dimensions. Our findings showed that the novel micelles had an ultrasmall particle size of 16–30 nm. We, for the first time, showed that the specific affinity of the novel linear RWrNM peptide to primary podocytes (24.9 ± 1.7 times of the free RhB uptake) through the αvβ3 integrin receptor mediation was comparable to that of B16F10 cells (24.4 ± 1.2 times of the free RhB uptake). In vivo studies showed that the novel ultrasmall micelles possessed a significant kidney-targeted effect, excellent podocyte colocalization effect, and GFB permeability at 49%–60 % in normal SD rats . Besides, the novel ultrasmall micelles decreased the plasma elimination half-life of Dexac to 1.62–2.09 h and showed good safety in vitro and in vivo. Both in vitro and in vivo results demonstrated the novel ultrasmall micelles could be used as a promising drug delivery strategy for actively targeted therapy of CKD.

✓ 已验证 DOI PubMed 高影响因子
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MOLECULAR PHARMACEUTICS · 2021 · IF 4.939

mPEG2k-PCLx Polymeric Micelles Influence Pharmacokinetics and Hypoglycemic Efficacy of Metformin through Inhibition of Organic Cation Transporters in Rats

Ying Zhang,Minghui Sun,Shuxin Jian,Jiangeng Huang,Chuyao Xiao,Xiangyu Zhang,Ruhao Hu,Luqin Si

Increasing evidence has shown that nanocarriers have effects on several efflux drug transporters. To date, little is known about whether influx transporters are also modulated. Herein, we investigated the impact of amphiphilic polymer micelles on the uptake function of organic cation transporters (OCTs) and the influence on the pharmacokinetics and pharmacodynamics of metformin, a well-characterized substrate of OCTs. Five types of polymeric micelles (mPEG2k-PCL2k, mPEG2k-PCL3.5k, mPEG2k-PCL5k, mPEG2k-PCL7.5k, and mPEG2k-PCL10k) were prepared to evaluate the inhibition of hOCT1-3-overexpressing Madin–Darby canine kidney cells. The mPEG2k-PCLx micelles played an inhibitory role above the critical micelle concentration. The inhibitory potency could be ranked as mPEG2k-PCL2k > mPEG2k-PCL3.5k > mPEG2k-PCL5k > mPEG2k-PCL7.5k > mPEG2k-PCL10k, which negatively declined with the increase of molecular weight of the hydrophobic segment. The inhibitory effects of polymeric micelles on the hOCT1 isoform were the most pronounced, with the lowest IC50 values ranging from 0.106 to 0.280 mg/mL. The mPEG2k-PCL2k micelles distinctly increased the plasma concentration of metformin and significantly decreased Vss by 35.6% (p < 0.05) after seven consecutive treatments in rats, which was interrelated with the restrained metformin distribution in the liver and kidney. The uptake inhibition of micelles on hepatic and renal rOcts also diminished the glucose-lowering effect of metformin and fasting insulin levels in the oral glucose tolerance test. Consistent with the inhibitory effects, the mRNA and protein levels of rOct1 and rOct2 were decreased in the liver, kidney, and small intestine. The present study demonstrated that mPEG2k-PCLx micelles could inhibit the transport function of OCTs, indicating a potential risk of drug–drug interactions during concomitant medication of nanomedicine with organic cationic drugs.

✓ 已验证 DOI PubMed 高影响因子
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Nanoscale · 2018 ·Vol. 10 ·期 6 ·2923-2935 · IF 7.233

Endogenous sialic acid-engineered micelles: a multifunctional platform for on-demand methotrexate delivery and bone repair of rheumatoid arthritis

Xiao-Ling Xu,Wei-Shuo Li,Xiao-Juan Wang,Yang-Long Du,Xu-Qi Kang,Jing-Bo Hu,Shu-Juan Li,Xiao-Ying Ying,Jian You,Yong-Zhong Du

Rheumatoid arthritis (RA) patients have suffered from the current drug therapeutic regimen because of its high toxicity and the absence of bone regeneration for existing erosion, seriously affecting the quality of life. Herein, a sialic acid-dextran-octadecanoic acid (SA-Dex-OA) conjugate was synthesized to form micelles with a 55.06 μg mL−1 critical micelle concentration. The obtained micelles can encapsulate a disease-modifying anti-rheumatic drug, methotrexate (MTX), with 4.28% (w/w) drug content, featuring sustained drug release behavior over 48 h. In vitro and in vivo studies showed that SA-Dex-OA micelles significantly improved accumulation and transportation through a combination of SA and E-selectin receptors in inflamed cells and arthritic paws highly expressing E-selectin. MTX-loaded SA-Dex-OA micelles not only significantly inhibited the inflammatory response, but also diminished the adverse effects of MTX, as reflected by the reduced alanine aminotransferase, aspartate aminotransferase, creatinine, and urea nitrogen levels. Most importantly, the bone mineral density in rats treated with MTX-loaded SA-Dex-OA micelles was significantly higher as compared to in those treated with free MTX and Dex-OA/MTX micelles (increasing from 391.4 to 417.4 to 492.7 mg cc−1), benefiting from the effects of endogenous sialic acid in promoting MC3T3-E1 cell differentiation and mineralization. It is anticipated that SA-based micelles with bone repair activities have great potential for RA treatment and other metabolic bone diseases with serious bone erosion.

✓ 已验证 DOI PubMed 高影响因子
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