Polymer Chemistry
·
2013
·Vol. 5
·期 8
·2801-2808
·
IF 5.231
Yu Zhang,Chunsheng Xiao,Mingqiang Li,Jianxun Ding,Chaoliang He,Xiuli Zhuang,Xuesi Chen
The linear-dendritic prodrug MPEG–b-PAMAM–LA/DOX was synthesized through modifying the linear methoxy poly(ethylene glycol)–block-dendritic poly(amidoamine) (MPEG–b-PAMAM) with lipoic acid (LA) and then conjugating doxorubicin (DOX) by an acid-labile hydrazone bond. The obtained amphiphilic prodrug self-assembled into nanosized spherically shaped micelles in deionized water, as characterized by transmission electron microscopy (TEM) and dynamic laser scattering (DLS). The micelles could be cross-linked using a catalytic amount of dithiothreitol (DTT). Compared with the non-cross-linked micellar nanoparticles (NPs) (NCL-NPs), the cross-linked NPs (CL-NPs) were more stable against dilution and high salt concentration. However, in the presence of 10 mM glutathione (GSH), the reducible CL-NPs swelled in a short time, as determined by DLS. In in vitro drug release experiments, the CL-NPs exhibited pH and reduction dual responsive DOX release behaviour. DOX was released slowly under physiological pH (7.4) and/or in the absence of reduced GSH, but was released quickly at endosomal pH (5.5) and in the presence of GSH (5 mM or 10 mM). Both the confocal laser scanning microscopy (CLSM) and flow cytometry (FCM) studies indicated that CL-NPs could be effectively taken up by the HeLa cells, and the conjugated DOX was efficiently released in response to the intracellular environment (low pH and high GSH concentration). In the MTT assay, CL-NPs could effectively inhibit the proliferation of HeLa cells and A549 cells. Thus, CL-NPs with superior stability, pH and reduction dual responsive drug release behaviour and good anti-cancer capability showed promise for anti-cancer treatment in the future.
研究领域:
药学
·
纳米技术
·
药物递送系统
·
癌症治疗
✓ 已验证
产品关联
DOI
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.
研究领域:
药学
·
纳米技术
·
生物医学工程
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2022
·Vol. 9
·期 32
·2203523
·
IF 17.521
Ming Shen,Chuanrong Chen,Qianqian Guo,Quan Wang,Jinghan Liao,Liting Wang,Jian Yu,Man Xue,Yourong Duan,Jiali Zhang
T-cell engagers (TCEs) represent a breakthrough in hematological malignancy treatment but are vulnerable to antigen escape and lack a vaccination effect. The “immunologically cold” solid tumor presents substantial challenges due to intratumor heterogeneity and an immunosuppressive tumor microenvironment (TME). Here, a methoxy poly(ethylene glycol) (mPEG)-masked CD44×PD-L1/CD3 trispecific T-cell nanoengager loaded with the STING agonist c-di-AMP (CDA) (PmTriTNE@CDA) for the treatment of triple-negative breast cancer (TNBC) is rationally designed. PmTriTNE@CDA shows tumor-specific accumulation and is preferentially unmasked in response to a weakly acidic TME to prevent on-target off-tumor toxicity. The unmasked CD44×PD-L1/CD3 trispecific T-cell nanoengager (TriTNE) targets dual tumor-associated antigens (TAAs) to redirect CD8+ T cells for heterogeneous TNBC lysis while achieving PD-L1 blockade. PmTriTNE synergized with CDA to transform the cold tumor into a hot tumor, eradicate the large established TNBC tumor, and induce protective immune memory in a 4T1 orthotopic tumor model without causing obvious toxicity. PmTriTNE@CDA shows potent efficacy in cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) mouse models. This study serves as a proof-of-concept demonstration of a nanobased TCEs strategy to expand therapeutic combinations that previously could not be achieved due to systemic toxicity with the aim of overcoming TNBC heterogeneity and immunotherapy resistance.
研究领域:
肿瘤学
·
免疫学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Discover Nano
·
2023
·Vol. 18
·期 1
·1-14
·
IF 0
Shao Runrun,Qiao Xiaofang,Cao Linlin,Man Jianliang,Guo Lingyun,Li Lanlan,Liu Wen,Li Lihong,Wang Bin,Guo Lixia,Ma Sufang,Zhang Boye,Wang Haojiang,Yan Lili
The development of nanoparticles capable of inducing reactive oxygen species (ROS) formation has become an important strategy for cancer therapy. Simultaneously, the preparation of multifunctional nanoparticles that respond to the tumor microenvironment is crucial for the diagnosis and treatment of tumors. In this study, we designed a Molybdenum disulfide (MoS 2 ) core coated with Manganese dioxide (MnO 2 ), which possessed a good photothermal effect and could produce Fenton-like Mn 2+ in response to highly expressed glutathione (GSH) in the tumor microenvironment, thereby generating a chemodynamic therapy (CDT). The nanoparticles were further modified with Methoxypoly(Ethylene Glycol) 2000 (mPEG-NH 2 ) to improve their biocompatibility, resulting in the formation of MoS 2 @MnO 2 -PEG. These nanoparticles were shown to possess significant Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) imaging capabilities, making them useful in tumor diagnosis. In vitro and in vivo experiments demonstrated the antitumor ability of MoS 2 @MnO 2 -PEG, with a significant killing effect on tumor cells under combined treatment. These nanoparticles hold great potential for CDT/photothermal therapy (PTT) combined antitumor therapy and could be further explored in biomedical research.
研究领域:
生物医学工程
·
纳米技术
·
癌症治疗
·
医学成像
✓ 已验证
DOI
Biomaterials Advances
·
2025
·
IF 6
Naiyu Wang,Shiqi Kang,Qi Zeng,Wu Xu,Yuanyuan Zhao,Xudong Shi,Ruijun Li
Limited ability of nerve regeneration and the formation of nerve adhesions result to poor outcomes of peripheral nerve injury (PNI) following surgical nerve repair. Currently, there is no efficient therapy for the improvement of functional recovery after surgical repair. Rapamycin (Rapa) has been found useful for promoting nerve regeneration through removing cellular debris at the early stages after PNI. However, its lower oral bioavailability and significant adverse effects limit its clinical application. In this study, we developed a biocompatible nerve wrap based on biocompatible monomethoxy poly (ethylene gly co l)-poly (lactic- co -glycolic acid) (mPEG-PLGA) for the local delivery of Rapa. The Rapa-mPEG-PLGA nerve wrap exhibited a rough surface and good hydrophilicity with strong mechanical strength. In vitro release studies revealed an initial rapid phase within the first 8 days, followed by a stable release about 10 days. The released Rapa remained its bioactivity to induce autophagy and promote cell migration. In a rat model of sciatic nerve transection and immediate repair, the implantation of Rapa-mPEG-PLGA nerve wrap significantly enhanced axonal regeneration and myelination. Furthermore, the nerve wraps effectively prevented the occurrence of nerve adhesions. Improved functional recovery was observed with Rapa-mPEG-PLGA membrane wrap post-surgery 4 weeks and 8 weeks. In summary, the Rapa-loaded mPEG-PLGA nerve wrap promoted nerve regeneration by releasing Rapa at the early stage after injury, and acted as a physical barrier to reduce nerve adhesions. This local dual-action strategy is a promising candidate for clinical translation in the treatment of PNI following surgical repair.
研究领域:
生物医学工程
·
神经科学
·
药理学
·
生物材料
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2018
·
IF 4.37
Menghao Shi,Xiufeng Zhao,Jiulong Zhang,Shuang Pan,Chunrong Yang,Ying Wei,Haiyang Hu,Mingxi Qiao,Dawei Chen,Xiuli Zhao
Introduction Specific polo-like kinase (PLK1) silencing with small interface RNA (siRNA) may be an effective approach for PLK1-overexpressed lung cancer. However, low siRNA concentration into cytoplasm of tumor tissue severely limits its application. Materials and methods In this study, a novel triblock copolymer methoxy poly(ethylene glycol)-poly(histidine)-poly(sulfadimethoxine) (mPEG-PHis-PSD, shorten as PHD) was synthesized and used to construct novel nonviral gene vector with cationic liposomes. Results The resulting hybrid nanoparticles (PHD/LR) loaded with siPLK1 possessed excellent physiochemical properties. In vitro study indicated that PHD/LR could be efficiently internalized into human lung adenocarcinoma A549 cells and downregulated PLK1 protein expression to induce cell apoptosis, which was attributed to pH-induced instantaneous dissociation, efficient endo/lysosomal escape arose from PHD copolymer. Furthermore, in vivo antitumor activity demonstrated that PHD/LR could efficiently accumulated into tumor tissue and silenced PLK1 expression to possess antitumor activity. Conclusion Taken all these together, PHD/LR was expected to be a suitable carrier for specific delivering siRNA for lung cancer therapy.
研究领域:
癌症研究
·
纳米技术
·
药学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2017
·
IF 7.504
Yajing Liu,Shaojia Zhu,Kaizhi Gu,Zhiqian Guo,Xiaoyu Huang,Mingwei Wang,Hesham M. Amin,Weihong Zhu,Ping Shi
Theranostic prodrug therapy enables the targeted delivery of anticancer drugs with minimized adverse effects and real-time in situ monitoring of activation of the prodrugs. In this work, we report the synthesis and biological assessment of the near-infrared (NIR) prodrug DCM-S-PPT and its amphiphilic copolymer (mPEG-DSPE)-encapsulated nanoparticles. DCM-S-PPT is composed of podophyllotoxin (PPT) as the anticancer moiety and a dicyanomethylene-4H-pyran (DCM) derivative as the NIR fluorescent reporter, which are linked by a thiol-specific cleavable disulfide bond. In vitro experiments indicated that DCM-S-PPT has low cytotoxicity and that glutathione (GSH) can activate DCM-S-PPT resulting in PPT release and a concomitant significant enhancement in NIR fluorescence at 665 nm. After being intravenously injected into tumor-bearing nude mice, DCM-S-PPT exhibited excellent tumor-activated performance. Furthermore, we have demonstrated that mPEG-DSPE as a nanocarrier loaded with DCM-S-PPT (mPEG-DSPE/DCM-S-PPT) showed even greater tumor-targeting performance than DCM-S-PPT on account of the enhanced permeability and retention effect. Its tumor-targeting ability and specific drug release in tumors make DCM-S-PPT a promising prodrug that could provide a significant strategy for theranostic drug delivery systems.
研究领域:
药学
·
生物医学工程
·
癌症研究
·
纳米技术
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscience and Nanotechnology Letters
·
2020
·Vol. 12
·期 7
·946-952
·
IF 1.128
Mou Fengping,Xiao Li,Xu Yuanqin
This study aims to investigate the therapeutic effect of a paclitaxel-loaded nano-drug (PTX-mPEGPLA) on oral squamous cell carcinoma (OSCC). PTX-mPEG-PLA nanoparticle (NP) was prepared by loading paclitaxel into the mPEG-PLA nanoparticle and purified by a thin-film hydration method.
C57BL/6 mice were used to establish a murine OSCC model. The mice were treated with saline control (G1), paclitaxel (G2), or PTX-mPEG-PLA NPs (G3). After 4 weeks of differential treatment, the saliva of mice in the G1, G2, and G3 groups was collected to detect the concentration of protein
markers of OSCC. Also, venous blood and cancer tissues of mice in the three groups were collected for drug concentration measurements. The paclitaxel concentration and retention in G3 mice were significantly higher and more prolonged than those in G2 mice, respectively (P < 0.05).
Compared to the level of OSCC protein markers in the saliva of mice in G1 and G2 that in G3 was the lowest. PTX-mPEG-PLA NPs demonstrates effective targeting in the treatment of oral squamous cell carcinoma in mice. It can deliver the drug to the cancerous tissues, increase the drug retention
in the same tissues, and effectively inhibit the proliferation and metastasis of malignant tumors.
研究领域:
肿瘤学
·
药理学
·
纳米技术
·
实验医学
✓ 已验证
DOI
高影响因子
LANGMUIR
·
2022
·
IF 4.331
Mingwei Guo,Zhifeng Zhao,Zhongyuan Xie,Weixin Wu,Wenjing Wu,Qinwei Gao
The isothermal crystallization behavior and corresponding morphology evolution of poly(d-lactic acid) (PDLA) blends with PLLA6.7k or MPEG-b-PLLA6.7k-g-glucose with different architectures and different PLLA-grafted copolymer contents were investigated. The formation of stereocomplexes (SCs) in between the chain branched structure of MPEG-b-PLLA6.7k-g-glucose and PDLA chains acting as the physical crosslinking points slows down the motion of PDLA chains, but the SCs could act as a heterogeneous nucleating agent for the late formation of homocrystals (HCs) in the blend system, accelerating the crystallization kinetics of HCs through enhancing the nucleation density. For PDLA/MPEG-b-PLLA6.7k-g-glucose blends, the mobility of SCs in the blend system and the nucleation density of SCs in the blends exhibit oppositional behavior during the isothermal crystallization at a Tc of 130 °C. The evolution of the crystal growth and structure during the isothermal crystallization process by rheometry has revealed the interesting role of the branched chains of MPEG-b-PLLA6.7k-g-glucose in the mechanism of the crystallization in PDLA blends.
研究领域:
材料科学
·
高分子化学
✓ 已验证
DOI
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2025
·
IF 4.6
Jing-Jing Qiao,Lu Fan,Jie-Li Zhou,Kai Wang
Cysteine (Cys) plays pivotal roles in redox homeostasis and metabolic regulation, with its dysregulation implicated in obesity-related hepatic disorders. Here, we developed a sulfur-substituted hemicyanine-based nanoprobe (Cys-NP) for photoacoustic imaging of hepatic Cys dynamics. The Cys-responsive molecular probe (Cys-MP) was encapsulated in mPEG-DSPE nanoparticles to overcome aqueous solubility limitations, yielding monodisperse nanoparticles with an average diameter of 28.7 nm and excellent colloidal stability. Sulfur substitution endowed the probe enhanced photoacoustic signals compared to oxygenated analogs, while selective Cys recognition triggered a bathochromic shift and yielded a detection limit of 0.13 μM. In high-fat-diet-induced obese mice, Cys-NP revealed significantly elevated hepatic Cys levels correlating with histopathological steatosis and hypercholesterolemia. This work establishes a nanotechnology-enabled strategy for mapping redox metabolism in metabolic diseases, offering both mechanistic insights and diagnostic potential.
研究领域:
纳米技术
·
分子成像
·
代谢性疾病
·
氧化还原生物学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
Materials Today Bio
·
2024
·
IF 8.7
Yannan Cheng,Yuanfang Huo,Yongle Yu,Ping duan,Xianzhen Dong,Zirui Yu,Qiang Cheng,Honglian Dai,Zhenyu Pan
Managing bone defects remains a formidable clinical hurdle, primarily attributed to the inadequate orchestration of vascular reconstruction and osteogenic differentiation in both spatial and temporal dimensions. This challenge persists due to the constrained availability of autogenous grafts and the limited regenerative capacity of allogeneic or synthetic bone substitutes, thus necessitating continual exploration and innovation in the realm of functional and bioactive bone graft materials. While synthetic scaffolds have emerged as promising carriers for bone grafts, their efficacy is curtailed by deficiencies in vascularization and osteoinductive potential. Nitric oxide (NO) plays a key role in revascularization and bone tissue regeneration, yet studies related to the use of NO for the treatment of bone defects remain scarce. Herein, we present a pioneering approach leveraging a photothermal-responsive system to augment NO release. This system comprises macromolecular mPEG-P nanoparticles encapsulating indocyanine green (ICG) (NO-NPs@ICG) and a mPEG-PA-PP injectable thermosensitive hydrogel carrier. By harnessing the synergistic photothermal effects of near-infrared radiation and ICG, the system achieves sustained NO release, thereby activating the soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) signaling pathway both in vitro and in vivo. This orchestrated cascade culminates in the facilitation of angiogenesis and osteogenesis, thus expediting the reparative processes in bone defects. In a nutshell, the NO release-responsive system elucidated in this study presents a pioneering avenue for refining the bone tissue microenvironment and fostering enhanced bone regeneration.
研究领域:
生物材料
·
组织工程
·
再生医学
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Electrochemical Science
·
2023
·
IF 1.5
Wenjuan Zhang,Lei Shi,Dongfang Niu,Heng Xu,Xinsheng Zhang,Shuozhen Hu
The effect of methoxypolyethylene glycol (mPEG) on chromium electrodeposition from a mixture of 1- butyl-3-methylimidazolium-bromide ([BMIM]Br) ionic liquid and water is studied. The addition of mPEG does not affect the two-step reduction process of Cr(III). With the presence of mPEG in the electrolyte, the diffusion coefficient decreases dramatically, and the resistance of the electrolyte and charge transfer increase, resulting in a reduced deposition rate and a smooth and crack-free coating surface. The hydrogen evolution reaction is suppressed, and more metallic Cr is deposited in the coating layer. Considering both the surface morphology and corrosion resistance, 80 mmol L -1 mPEG is the optimum concentration for smooth and pinhole-free chromium electrodeposition in the mixture of [BMIM]Br ionic liquid and water.
研究领域:
电化学
·
材料科学
·
表面工程
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）