Materials Today Communications
·
2019
·
IF 1.859
Henan Wang,Zeyu Li,Shuting Lu,Chunyu Li,Wancheng Zhao,Yuliang Zhao,Shuling Yu,Ting Wang,Tiedong Sun
Biocompatibility and targeted therapy are the demand by modern chemotherapy drugs. Meanwhile, the utilizations of biopolymer or environmentally friendly polymer are also the key issues for sustainable development. We have constructed a new drug delivery system with targeted and controlled release capabilities. It has been confirmed that an environmentally friendly polymer (CMC- g -PLA) obtained by grafting polylactic acid on a carboxymethyl cellulose biopolymer has an amphiphilic property and is easy to form micelles , thereby being useful as a hydrophobic drug carrier. In order to have the function of targeted therapy, anti-EpCAM antibody was anchored on the polymer chain of carboxymethyl cellulose by amidation reaction. Doxorubicin and HepG2 cells were used as the model anticancer drug and tumor targeting cells, respectively. The nano scale core-shell structure, critical micelle concentration , drug loading and encapsulation efficiency were studied by TEM, pyrene fluorescent probe method and ultraviolet standard curve method, respectively. Furthermore, the pH induced release function experiments, cytotoxicity experiments and in vivo tumor treatments experiments on mice. The results show that the drug carrier with antibody prepared by us can effectively deliver hydrophobic drugs to specific tumor sites and increase the effect of tumor treatment. This versatile design provides a new solution for future cancer treatments.
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高影响因子
POLYMER
·
2016
·
IF 3.586
Qinglai Yang,Changyu He,Zhen Zhang,Lianjiang Tan,Bingya Liu,Zhenggang Zhu,Zhifeng Shao,Bing Gong,Yu-Mei Shen
Redox-responsive micelles self-assembled from triblock copolymers of poly( l -lactic acid)-poly(ethylene glycol)-poly( l -lactic acid) ( PLA-PEG-PLA) with double-disulfide linkage in the backbone were synthesized and characterized by proton nuclear magnetic resonance ( 1 H NMR) and size exclusion chromatography (SEC), in which both PEG ( M n = 1000, 2000 and 4000 g mol −1 ) and PLA ( M n = 1600 g mol −1 ) have different molecular weights respectively. The triblock copolymers PLA 3000 -PEG 2000 -PLA 3000 and PLA 3000 -PEG 4000 -PLA 3000 can self-assemble into flower-like micelles in aqueous media with average diameters 110 nm and 43 nm and lower critical micelle concentrations (CMC) 0.017 and 0.014 mg mL −1 respectively compared with that of diblock copolymers. Moreover, in vitro drug release analyses indicated that reductive environment can result in triggered drug release profiles. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl- 2-H-tetrazolium bromide (MTT) assay in vitro showed no significant cytotoxicity as NIH 3T3 cells incubated in the micelles even when the concentrations up to 1000 μg/mL. Additionally fluorescence microscopy measurements and MTT assay demonstrated that the micelles exhibited a faster drug release and higher cellular proliferation inhibition due to the effect of intracellular reduction responsiveness compared with that of diblock copolymers. The above results suggest that the reduction-responsive, biodegradable and biocompatibility micelles could provide a platform to construct potential drug delivery systems for cancer therapy.
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INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2015
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IF 3.65
Zhi-qiang Yuan,Ji-zhao Li,Yang Liu,Wei-liang Chen,Shu-di Yang,Chun-ge Zhang,Wen-jing Zhu,Xiao-feng Zhou,Chun Liu,Xue-nong Zhang
This study aimed to prepare efficient cRGDyK peptide-decorated micelles for the targeted therapy of non-small-cell lung cancer (NSCLC). An amphiphilic copolymer N -succinyl-palmitoyl-chitosan (SPCS) was synthesized and characterized. cRGDyK peptide is a ligand that can target tumors via specific binding integrin receptor overexpressed on tumor neovascularization and cells. cRGDyK-functionalized SPCS micelles loaded with paclitaxel (PTX/cRGDyK-SPCS) were prepared by film dispersion method and then characterized according to morphology, size, and zeta potential . PTX/cRGDyK-SPCS micelles presented pH-triggered drug release behavior under acidic conditions. The accumulation of micelles detected by laser confocal fluorescence microscopy and flow cytometry showed that cRGDyK-SPCS micelles were easily taken up by A549 cells marked with the luciferase gene (luc-A549). Meanwhile, co-localization of the micelles and lysosomes was recorded dynamically using a live cell station. MTT assays and cell apoptosis studies revealed that cell viability was significantly inhibited by PTX/cRGDyK-SPCS micelles. More importantly, in vivo animal studies showed that cRGDyK-SPCS micelles mainly accumulated in the orthotopic tumor site. PTX/cRGDyK-SPCS micelles exhibited better anti-tumor activity in subcutaneous and orthotopic lung tumors compared with PTX/SPCS micelles and Taxol ® . These results suggested that PTX/cRGDyK-SPCS micelles had better cancer targeting capacity and superior anti-tumor efficacy. Thus, these micelles have great potential as novel carriers in delivering anti-tumor drugs.
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高影响因子
LASERS IN MEDICAL SCIENCE
·
2025
·Vol. 40
·期 1
·1-25
·
IF 2.4
Abd El-Kaream Samir Ali,Hamoda Safia Ali Hussein,El Kholey Sohier Mahmoud,El-sharkawy Awatef Mohamed
Sono-photodynamic therapy (SPDT) has attracted a lot of interest as a cutting-edge therapeutic strategy in the field of cancer treatment. The essential part of SPDT is the sensitizer, which under laser photon and pulsed cavitation ultrasound sono-irradiation may transform sono and photo- energy into cytotoxic molecules. Photon absorption, targeting, penetration, and oxygen dependence remain challenges in sono- -photosensitizer (SPs) design. Rapid advancements in material science have prompted the creation of several SPs that create cytotoxic species with great selectivity, safety, and noninvasiveness for the treatment of tumors. The current study aims to provide an advanced method of activated cancer treatment by using pulsed cavitation to assist the delivery of cardamom, pistacia and laurel conjugated micelles nanoparticles (CPL-Micelle NP) for the sono-photodynamic lymphoma in vivo and in vitro treatment. Human lymphoma cells (U-937) were used in the in vitro study, and the in vivo application groups of the study protocol were Swiss albino mice treated with 9,10-Dimethyl-1,2-Benzanthracene (DMBA) only; they were not given any treatment to induce lymphoma. The study treatment protocol started only after lymphoma induction, and involved daily administration of CPL-Micelle NP as SPDT sensitizer whether or not to be exposed to photo- (IRL) or sono- (US) or a combination of them for three minutes for a period of two weeks. Indicated that Micelle NP is a useful CPL delivery mechanism that targets lymphoma cells directly. Furthermore, CPL-Micelle NP is a promising SPS that, when used in conjunction with SPDT, can be very effective in in vitro treating lymphoma-U-937 (in a dose-dependent manner cell viability declined, an increase in the cells population during the S and G2/M phases indicates that the cell cycle was arrested, and an increase in cell population in the Pre-G, autophagic cell death, as well as necrosis and early and late apoptosis, indicate that cell death was induced) and DMBA-Lymphoma-induced mice in vivo (induced antiproliferative genes, repressed antiangiogenic and antiapoptotic genes), successfully slowing the growth of tumors and even killing cancer cells, as well as lowering oxidative stress malondialdehyde (MDA), improving the functions of the kidneys, liver, and enzymatic and non enzymatic antioxidants. SPDT, the photo- or sono- chemical CPL activation mechanism, and the antioxidant capacity of non-activated CPL can all be linked to this process. On the bases of the findings, CPL-Micelle NP shows a great promise as a novel, efficient selective delivery system for localized SPDT-activated lymphoma treatment.
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高影响因子
JOURNAL OF DRUG TARGETING
·
2025
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IF 3.9
Jiaying Li,Tingyuan Li,Mingjie Gong,Xiaowen Wang,Qinyang Hua,Xia Jiang,Qilong Wang,Elmurat Toreniyazov,Jiangnan Yu,Xia Cao,Michael Adu-Frimpong,Ximing Xu
Phloretin exhibits strong antioxidant and anti-ageing properties by inhibiting mitochondrial oxidation of glutamate, succinic acid, and ascorbic acid. However, its clinical application is limited by poor aqueous solubility and low oral bioavailability. To enhance its bioavailability and efficacy, we incorporated phloretin into nano-micelles (phloretin-MM) using the thin film dispersion method. Characterisation revealed that the optimal formulation had TPGS and Pluronic F68 in a 4:1 ratio as the excipients, which resulted in spherical micelles with an average particle size of 33.28 nm and an encapsulation efficiency of 71.2 ± 0.48%. The in vitro release profile showed that the phloretin-MM showed significantly higher cumulative release rates than free phloretin across various pH conditions, while the pharmaceutical analysis in rats indicated that phloretin-MM significantly improved the oral bioavailability of phloretin (about 5 folds) in circulation. Additionally, through the analysis of the staining of zebrafish under light microscopy and the average gray value, it can be concluded that phloretin has anti-ageing drug effect, and phloretin-MM is better than free phloretin. These findings suggest that TPGS/Pluronic F68-modified phloretin-MM could serve as an excellent nano-drug carrier system, potentially enhancing the solubility, bioavailability, and anti-ageing effects of phloretin for broader clinical applications.
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INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2022
·
IF 6.51
Tengteng Yuan,Shujie Lv,Wei Zhang,Yanan Tang,Hong Chang,Zihan Hu,Liang Fang,Jiaojiao Du,Sifan Wu,Xinli Yang,Yangfu Guo,Ruihan Guo,Zongrui Ge,Lei Wang,Caiyun Zhang,Rulin Wang,Weidong Chen
Paeoniflorin (PF) has a certain therapeutic effect on cholestasis liver injury. To further improve the bioavailability of PF and play its pharmacological role in liver protection, PF-phospholipid complex micelles (PF-PLC micelles) were prepared based on our previous research on PF-PLC. The protective effects of PF and PF-PLC micelles on cholestasis liver injury induced by 17α-ethynylestradiol (EE) were compared, and the possible mechanisms were further explored. Herein, we showed that PF-PLC micelles effectively improved liver function, alleviated liver pathological damage, and localized infiltration of inflammatory cells. Mechanism studies indicated that PF-PLC micelles treatment could suppress the TLR4/MyD88/NF-κB pathway, and further reduce the levels of pro-inflammatory factors. Meanwhile, our experimental results demonstrated that the beneficial effect of PF-PLC micelles on EE-induced cholestasis may be achieved by the upregulation of nuclear receptors and metabolic enzymes (PXR/CAR/UGT1A1). All these results indicate that PF-PLC micelles have great potential in the treatment of cholestatic liver disease.
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高影响因子
RSC Advances
·
2016
·Vol. 6
·期 105
·103843-103850
·
IF 3.289
Aitang Zhang,Aihua Li,Yao Wang,Mengli Liu,Hongjing Ma,Zhongqian Song,Jingquan Liu
Mesoporous carbon nanoparticles (MCNs) were prepared through a series of annealing procedures using well-controlled diblock copolymer micelles as precursors. The micelles were prepared from poly(acrylonitrile)-block-poly(methylmethacrylate) (PAN-b-PMMA), and synthesized via reversible addition–fragmentation chain transfer (RAFT) polymerization. The RAFT-controlled synthesis of block copolymer, PAN-b-PMMA was conducted either in solution or emulsion conditions. It was found that micelles with well-defined morphology could be directly formed from the emulsion polymerization. The as-synthesized micelles containing hydrophilic PAN corona as the carbon source and hydrophobic PMMA core as the sacrificing template underwent a microphase-separation process to form a nanostructure at 250 °C, followed by carbonization at 800 °C to afford MCNs. What's more, the MCNs based supercapacitor exhibited a good capacitance value of 220 F g−1 and an excellent cycling performance of 91% capacitance retention after 10 000 cycles. The as-prepared MCNs are envisioned to provide broad practical applications in the fields of energy storage and nanotechnology.
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高影响因子
PHYTOMEDICINE
·
2026
·
IF 11.3
Huihui Shi,Feifei Li,Meng Wang,Mengyue Zhu,Bei Deng,Dongpo Li,Yuming Yao,Meiling Zhou
The FA-modified pH-sensitive micelles (FA-PM@QCT/PTX) can enhance tumor targeting and lysosome-triggered drug release. • The system reverses chemotherapy resistance via the synergistic action of co‑delivered quercetin and paclitaxel, significantly enhancing cytotoxicity and inducing apoptosis in drug‑resistant cancer cells. • The system demonstrates potent antitumor efficacy with excellent biocompatibility in vivo , markedly inhibiting tumor growth while showing minimal systemic toxicity. Background Chemotherapy remains a major challenge in the effective treatment of non-small cell lung cancer (NSCLC), particularly due to chemotherapy resistance. Natural products, including Chinese herbal extracts, have shown potential for improving chemotherapy sensitivity, but their clinical application is limited by poor tumor targeting and insufficient in vivo stability. Purpose This study aimed to improve PTX-based treatment against resistant NSCLC by developing a FA receptor-targeted pH-sensitive co-delivery system for QCT and PTX. Study design A novel FA receptor-targeted pH-responsive nano-delivery system, FA-PM@QCT/PTX, was constructed and evaluated using PTX-resistant A549/Taxol cells and A549/Taxol tumor-bearing mouse models. Methods FA-PM@QCT/PTX was prepared and characterized in terms of particle size, PDI, zeta potential, encapsulation efficiency, and drug-loading content. In vitro pH-responsive release, cellular uptake, QCT/PTX synergism, cytotoxicity, apoptosis, cell-cycle distribution, P-gp expression, PI3K/Akt signaling, apoptosis-related proteins, and intracellular PTX retention were evaluated in A549/Taxol cells. Pharmacokinetics, tissue distribution, antitumor efficacy, survival benefit, and preliminary systemic safety were further assessed in A549/Taxol tumor-bearing mice. Results FA-PM@QCT/PTX showed a particle size of 166.75 ± 4.10 nm, a PDI of 0.14 ± 0.03, and a zeta potential of -6.34 ± 0.52 mV. The encapsulation efficiencies were 82.48 ± 3.82% for QCT and 84.17 ± 1.21% for PTX, with drug-loading contents of 3.64 ± 0.17% and 3.59 ± 0.11%, respectively. The self-assembled micelles could be internalized by tumor cells via FA receptor-mediated uptake and promote drug release under acidic lysosomal conditions. Chou-Talalay analysis showed that QCT enhanced the inhibitory effect of PTX on A549/Taxol cells, and the actual PTX:QCT molar ratio in FA-PM@QCT/PTX was approximately 1:3, which remained synergistic with a combination index (CI) value of 0.927 ± 0.021. Mechanistically, FA-PM@QCT/PTX reduced P-gp expression, enhanced intracellular PTX retention, suppressed PI3K/Akt signaling, and promoted apoptosis-related pathway activation. In vivo , FA-PM@QCT/PTX improved tumor drug accumulation and prolonged the median survival of A549/Taxol tumor-bearing mice to 52 days without obvious systemic toxicity. Conclusions These results suggest that FA-PM@QCT/PTX may provide a promising co-delivery strategy for improving PTX-based treatment against resistant NSCLC. Download: Download high-res image (371KB) Download: Download full-size image
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DRUG METABOLISM AND DISPOSITION
·
2026
·
IF 3.6
Jiayi Yao,Jiaqi Wang,Peipei Bu,Kexin Liu,Mingyang Zhao,Jingkai Gu,Xiangjun Meng
Fluorescent probes are extensively used for tracking the in vivo behavior of nanocarriers. However, the impact of fluorescent probes on the in vivo fate of nanomedicines remains uncertain. Potential interference from the probes may lead to misleading conclusions. This study investigated the influence of a commonly used fluorescent probe, DiI, on the in vivo fate of paclitaxel (PTX)-loaded polymeric micelles (PMs) in rats. The drug release kinetics of PTX-loaded PMs (PTX-PM) with DiI/PTX co-loaded PMs (DiI/PTX-PM) in rat plasma was quantitatively compared. The results indicate that co-encapsulation with DiI significantly exacerbated drug release and altered the protein binding of PTX through competitive binding, resulting in an increased proportion of free PTX. DiI enhanced diffusion-driven drug leakage without affecting the micelle dissociation kinetics. Notably, DiI inhibited elimination and increased the systemic exposure of both the free micelle material and the nanocarrier. This study provides evidence that DiI can potentially interfere with the in vivo fate of both the therapeutic payload and the nanocarrier, highlighting the necessity for rigorous validation when employing it for nanocarrier tracking.
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高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2026
·
IF 8.7
Ye-Fei Ruan,Jin-Hui Wang,Wen-Da Zhong,Lin Qiu
Targeting mitochondrial dysfunction in inflamed lung vessels addresses a key challenge in acute lung injury treatment, where current therapies lack precision and efficacy. • We develop smart nanoparticles that actively seek out injured blood vessels and release medicine only where oxidative stress is high, enabling enhanced mitochondrial repair. • This strategy markedly improves lung function and survival in mice with acute lung injury, demonstrating a promising approach for treating severe pulmonary inflammation. Acute lung injury (ALI) is a life-threatening condition with complex pathogenesis. Mitochondrial dysfunction in pulmonary vascular endothelial cells serves as a central hub, driving oxidative stress, inflammation, and barrier disruption. Existing treatments are limited by poor targeting and insufficient efficacy. To address this, we engineered a novel dual-targeting nanoplatform, P-selectin-directed and ROS-responsive fucoidan micelles loaded with the mitochondrial modulator Mitochonic Acid 5 (Fuc-TP@MA-5). Here we show that this system actively homes to inflamed lung endothelium via fucoidan-P-selectin binding and selectively releases MA-5 within the high-ROS microenvironment via thioketal linker cleavage. This enhanced delivery potently restores mitochondrial membrane potential and ATP production, scavenges excess ROS, and inhibits endothelial apoptosis. Consequently, Fuc-TP@MA-5 significantly attenuates pulmonary edema, vascular hyperpermeability, and inflammatory cytokine storm in a murine model of LPS-induced ALI, outperforming free MA-5. Our work establishes a targeted mitochondrial functional improvement strategy, offering a promising and intelligent nanotherapeutic paradigm for treating ALI and other vascular inflammatory disorders. Download: Download high-res image (166KB) Download: Download full-size image
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高影响因子
MOLECULES
·
2022
·Vol. 27
·期 9
·3016
·
IF 4.927
Fangjun Liu,Dun Wang,Jiaqi Wang,Liwei Ma,Cuiyun Yu,Hua Wei
Bottlebrush copolymers with different chemical structures and compositions as well as diverse architectures represent an important kind of material for various applications, such as biomedical devices. To our knowledge, zwitterionic conjugated bottlebrush copolymers integrating fluorescence imaging and tumor microenvironment-specific responsiveness for efficient intracellular drug release have been rarely reported, likely because of the lack of an efficient synthetic approach. For this purpose, in this study, we reported the successful preparation of well-defined theranostic zwitterionic bottlebrush copolymers with unique brush-on-brush architecture. Specifically, the bottlebrush copolymers were composed of a fluorescent backbone of polyfluorene derivate (PFONPN) possessing the fluorescence resonance energy transfer with doxorubicin (DOX), primary brushes of poly(2-hydroxyethyl methacrylate) (PHEMA), and secondary graft brushes of an enzyme-degradable polytyrosine (PTyr) block as well as a zwitterionic poly(oligo (ethylene glycol) monomethyl ether methacrylate-co-sulfobetaine methacrylate) (P(OEGMA-co-SBMA)) chain with super hydrophilicity and highly antifouling ability via elegant integration of Suzuki coupling, NCA ROP and ATRP techniques. Notably, the resulting bottlebrush copolymer, PFONPN9-g-(PHEMA15-g-(PTyr16-b-P(OEGMA6-co-SBMA6)2)) (P2) with a lower MW ratio of the hydrophobic side chains of PTyr and hydrophilic side chains of P(OEGMA-co-SBMA) could self-assemble into stabilized unimolecular micelles in an aqueous phase. The resulting unimolecular micelles showed a fluorescence quantum yield of 3.9% that is mainly affected by the pendant phenol groups of PTyr side chains and a drug-loading content (DLC) of approximately 15.4% and entrapment efficiency (EE) of 90.6% for DOX, higher than the other micelle analogs, because of the efficient supramolecular interactions of π–π stacking between the PTyr blocks and drug molecules, as well as the moderate hydrophilic chain length. The fluorescence of the PFONPN backbone enables fluorescence resonance energy transfer (FRET) with DOX and visualization of intracellular trafficking of the theranostic micelles. Most importantly, the drug-loaded micelles showed accelerated drug release in the presence of proteinase K because of the enzyme-triggered degradation of PTyr blocks and subsequent deshielding of P(OEGMA-co-SBMA) corona for micelle destruction. Taken together, we developed an efficient approach for the synthesis of enzyme-responsive theranostic zwitterionic conjugated bottlebrush copolymers with a brush-on-brush architecture, and the resulting theranostic micelles with high DLC and tumor microenvironment-specific responsiveness represent a novel nanoplatform for simultaneous cell image and drug delivery.Keywords:brush-on-brush;zwitterionic;enzyme-responsive;theranostic;FRET
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高影响因子
International Journal of Nanomedicine
·
2022
·
IF 7.033
Zemin Hou,Wencheng Zhou,Xi Guo,Rui Zhong,Ao Wang,Jiehua Li,Ying Cen,Chao You,Hong Tan,Meng Tian
Background The main challenge of polymeric micelles as drug delivery systems is that the actual delivery efficiency is not as high as expected, which is closely related with the interactions with the complex biological environments such as blood components, phagocytosis, and biodistribution. Herein, we expect to understand these concerns for the clinically relevant micelles that composed of methoxypolyethylene glycol (MPEG) with identical chain length And poly(ε-caprolactone) (PCL) with tunable chain length (PCL n -MPEG) (n=20, 30, and 40) wherein doxorubicin was encapsulated as a model drug. Methods The doxorubicin-loaded PCL n -MPEG micelles were prepared by a dialysis method and characterized by dynamic light scattering and transmission electron microscopy. The surface PEG density and chain conformation were investigated by dissipative particle dynamics simulation. The stability of the micelles was detected by nanoparticle tracking analysis. The effects of PCL chain length on the blood components, phagocytosis, and biodistribution were assayed in vitro and in vivo. Results The micelles exhibited spherical morphology with a diameter about 30nm. The PEG chain conformation from "mushroom-like" to "brush-like" was evident. The micelles have no remarkable effect on the red blood cells, blood coagulation, and platelet activation. Interestingly, the protein adsorption was affected and dependent on the chain conformation, with lowest adsorption for PCL 30 -MPEG, which also has the loWest phagocytosis. The stability of the micelles was in the order of PCL 40 -MPEG>PCL 30 -MPEG>PCL 20 -MPEG which was dependent on the PCL chain length. The micelles mainly accumulated in liver, with the order consistent with their stability, indicating that, besides the phagocytosis, the stability of the micelle plays an important role in biodistribution as well. The related mechanisms were proposed and discussed. Conclusion Manipulating the PEG/PCL ratio of the micelle is an effective approach to modulate the protein adsorption, phagocytosis, and biodistribution, which may be a prerequisite for clinical applications.
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高影响因子
危险品化学品经营许可证（带存储）