BIOMACROMOLECULES
·
2021
·
IF 6.988
Panpan Song,Nannan Song,Li Li,Minghao Wu,Zhongxia Lu,Xia Zhao
Glioblastoma (GBM) is a fatal brain tumor with poor prognosis. Blood–brain barrier (BBB) prevents the effective delivery of chemotherapeutic agents to GBM. Herein, we developed a pH/reduction-sensitive carboxymethyl chitosan nanogel (CMCSN) modified by targeting peptide angiopep-2 (ANG) and loaded with doxorubicin (DOX). The multifunctional nanogel (DOX-ANG-CMCSN) exhibited good pH and reduction sensitivity, ideal stability, and biocompatibility. Its hydrodynamic diameter was 190 nm, drug loading was 12.7%, and the cumulative release rate of 24 h was 82.3% under the simulated tumor microenvironment. More importantly, the modification of ANG significantly enhanced BBB penetration and tumor targeting ability both in vivo and in vitro. DOX-ANG-CMCSN achieved 2–3-fold higher uptake and an enhanced antitumor activity compared with nontargeted DOX-CMCSN. Therefore, the targeted nanogels with the pH/reduction dual-stimuli response may provide a promising platform for GBM-targeted chemotherapy.
研究领域:
药学
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纳米技术
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神经肿瘤学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2019
·Vol. 8
·期 5
·1290-1297
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IF 5.251
Xiao-Xiao Shi,Wei-Min Miao,Di-Wen Pang,Jia-Si Wu,Qi-Song Tong,Jia-Xian Li,Jia-Qi Luo,Wen-Yu Li,Jin-Zhi Du,Jun Wang
Primary central nervous system lymphoma (PCNSL) is a rare brain tumor. Its therapeutic efficacy is much lower than that of traditional lymphoma, largely due to the presence of the blood–brain barrier (BBB), which hinders the effective drug delivery and deposition on the disease site. Angiopep-2 (ANG) can target low-density lipoprotein receptor-related protein (LRP) on the surface of brain capillary endothelial cells (BCECs) and exhibits high BBB transport capability. In this study, we designed an ANG conjugated poly(ethylene glycol)-b-poly(ε-caprolactone) (PEG-b-PCL) (APP) nanoparticle to deliver doxorubicin (DOX) for the treatment of PCNSL. Our data indicated that the targeted APP nanoparticles showed significantly increased cellular uptake by BCECs compared with the control nanoparticles. In the intracranial SU-DHL-2-LUC lymphoma xenograft mice model, APP enhanced drug deposition in tumor tissues, and DOX-loaded APP (APP@DOX) exhibited a better therapeutic effect than free DOX and nontargeted PP@DOX, which significantly prolonged the survival time of mice.
研究领域:
肿瘤学
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神经科学
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药学
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纳米技术
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG TARGETING
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2025
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IF 3.9
Jing Jiang,Yue Xing,Shumeng Liu,Yue Na,Xia Lei,Fang Geng,Yafeng Zhang,Lihong Yang,Ning Zhang
Naringin (4',5,7-trihydroxyflavanone-7-rhamnoglucoside, NG), a potential treatment for Alzheimer’s disease (AD), has strong neuroprotective effects but is limited by poor solubility, low bioavailability, and limited brain accumulation. To address these issues, we developed ANG-NG-NPs, a novel NG-loaded poly (ethylene glycol)-poly(ε-caprolactone) copolymers (PEG-PCL) nanoparticle modified with the brain-targeting peptide Angiopep-2 (TFFYGGSRGKRNNFKTEEY, ANG). ANG-NG-NPs exhibited an average size of 126.1 ± 4.50 nm, a zeta potential of -2.97 ± 0.29 mV, 73.43% ± 0.80% encapsulation efficiency (EE), and 24.68% ± 0.45% drug loading capacity (LC). In vitro release studies confirmed its sustained-release properties. In vivo, ANG-NG-NPs extended NG’s circulation time and increased brain uptake. Notably, ANG-NG-NPs restored learning and memory in APP/PS1 mice, improved hippocampal cell health, and reduced hyperphosphorylated tau protein (p-Tau) expression. These findings suggest ANG-NG-NPs as a promising brain-targeting system for treating central nervous system disorders.
研究领域:
药剂学
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神经科学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Science of Advanced Materials
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2019
·Vol. 11
·期 7
·1008-1018
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IF 1.158
Pan Hongtao,Zhang Yanjie,Zhao Xiangkun,Zhou Hongsuo
In this study, glutamic acid and sugar are selected as raw materials to produce glutamic acid-sucrose fluorescent carbon dot material (CDs-N) according to a certain proportion. In order to prolong the time of biological detection, CDs-N-PEG is modified by PEG. Considering that melanoma
will enter the brain, Angiopep-2 ligand and RGD circulating ligand are selected to further obtain CDs-N-PEG-ANG and CDs-N-PEG-RGD. The material is characterized, the fluorescence spectrum is tested, the tyrosinase detection test is designed, the B16F10 cells in vivo are selected for
the biotoxicity test, and the tyrosinase and melanoma detection are extended to the organism. In this study, mice and zebrafish are selected as the research objects. The experimental results show that the fluorescent carbon dots designed in this study can detect tyrosinase well. With the increase
of concentration and reaction time, the fluorescent carbon dots fluorescence intensity corresponding to the site will continue to increase. In the toxicity test of B16F10 cells, the fluorescent carbon dot material shows little toxicity, indicating that the material has good biocompatibility.
Tyrosinase activity is well detected in zebrafish. By comparing B16F10 cells and Hela cells expressed with different tyrosinases, melanoma in mice is preliminarily detected. In this study, tyrosinase is used to detect melanoma and tyrosinase-based biomarkers are used to provide a feasible
method for the preliminary diagnosis of melanoma.
研究领域:
生物医学
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材料科学
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肿瘤学
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DOI
高影响因子
MOLECULAR PHARMACEUTICS
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2019
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IF 4.396
Jiaoyang Tao,Weidong Fei,Hongxia Tang,Chaoqun Li,Chaofeng Mu,Hongyue Zheng,Fanzhu Li,Zhihong Zhu
The poor capability of drugs to permeate through the blood–brain barrier (BBB) and further release inside glioma greatly limits the curative effects of glioma chemotherapies. In this study, we prepared angiopep-2-conjugated liposome-silica hybrid nanovehicles for targeted delivery and increased the permeation of arsenic trioxide (ATO) in glioma. Polyacrylic acid (PAA) was grafted on mesoporous silica nanoparticles (MSN) for pH-sensitive release and supporting the lipid membrane. The prepared “core–shell” nanovehicles (ANG-LP-PAA-MSN) were characterized with uniform size, high drug loading efficiency (8.19 ± 0.51%), and superior pH-sensitive release feature. From the experiments, the enhanced targeted delivery of ATO by ANG-LP-PAA-MSN (ANG-LP-PAA-MSN@ATO) was evidenced by the improvement of transport, enhanced cellular uptake, and apoptosis in vitro. In addition, the pharmacokinetic study was creatively carried out through the blood–glioma synchronous microdialysis and revealed that the half-life (t1/2) of blood and glioma tissue in the ANG-LP-PAA-MSN@ATO treatment group was extended by 1.65 and 2.34 times compared with the ATO solution group (ATO-Sol). The targeting efficiency of ANG-LP-PAA-MSN@ATO (24.96%) was dramatically stronger than that of the ATO-Sol (5.94%). Importantly, ANG-LP-PAA-MSN@ATO had a higher accumulation (4.6 ± 2.6% ID per g) in tumor tissues and showed a better therapeutic efficacy in intracranial C6 glioma bearing rats. Taken together, the blood–glioma synchronous microdialysis was successful used for the pharmacokinetic study and real-time monitoring of drug concentrations in blood and glioma; ANG-LP-PAA-MSN could be a promising targeted drug delivery system for glioma therapy.
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DOI
PubMed
高影响因子
Green Processing and Synthesis
·
2023
·Vol. 12
·期 1
·
IF 4.3
Xin Zhang,Xutong Zhu,Lifa Huang,Zupeng Chen,Yuchen Wang,Yajun Liu,Ruihan Pan,Ling Lv
Tanshinone IIA has a potential therapeutic effect on cerebral ischemia/reperfusion injury (CIRI). In this study, tanshinone IIA was encapsulated in poly(lactic- co -glycolic acid)-block-poly (ethylene glycol)-carboxylic acid (PLGA-PEG-COOH) nanoparticles, and its therapeutic efficacy on CIRI was investigated. Morphology and dynamic light scattering analyses were performed to identify and optimize nano-formulations. A drug release test was conducted using the dialysis method. The cytotoxic effect of tanshinone IIA on human neuroblastoma cells (SH-SY5Y) and brain endothelial capillary cells (hCMEC/D3) was measured using the MTT assay. The protective effect of PLGA-PEG-COOH-encapsulated tanshinone IIA against CIRI was evaluated in oxygen and glucose deprivation/reoxygenation-induced SH-SY5Y/IR cells and middle cerebral artery occlusion (MCAO) rats. Results showed that PLGA-PEG-COOH-encapsulated tanshinone IIA promoted viability and inhibited apoptosis of SH-SY5Y/IR cells ( P < 0.01). Moreover, PLGA-PEG-COOH-encapsulated tanshinone IIA facilitated the invasion of SH-SY5Y/IR cells and repressed inflammation in MCAO rats ( P < 0.01). Noteworthy, PLGA-PEG-COOH-encapsulated tanshinone IIA combined with angiopep-2 peptide presented a better inhibitory effect on CIRI than tanshinone IIA alone ( P < 0.01). Angiopep-2 peptide contributes to traversing blood–brain barrier by recognizing lipoprotein-related protein expressed in the brain capillary endothelial cells. In conclusion, PLGA-PEG-COOH-encapsulated tanshinone IIA plus angiopep-2 peptide holds promising therapeutic potential toward CIRI.
研究领域:
药学
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神经科学
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纳米技术
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药理学
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产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Yaxin Qin,Xiaoyan Sun,Zhicheng Zhang,Yufan Yang,Qi Dai,Xin Tan,Ruolin Jiang,Xiaoyan Bao,Linjie Wu,Changran Geng,Yuanhao Liu,Xiaoping Sun,Xingyan Liu,Minoru Suzuki,Qinchun Wei,Min Han
Glioblastoma is a highly malignant brain tumor with few available therapeutic options, for which boron neutron capture therapy (BNCT) has emerged as a promising precision radiotherapy approach. However, its efficacy remains suboptimal due to inadequate tumor targeting of boron agents and lack of in vivo visualization. Herein, a gadolinium–boron integrated lipid nanocarrier (BPA-F&DOTA-Gd@LIPO-ANG) was developed for targeted boron delivery and MRI-guided BNCT. BPA-F and DOTA-Gd were coloaded into lipid nanocarriers using a microfluidic system, with Angiopep-2 modification to enhance blood–brain barrier penetration and glioma targeting. Following cellular uptake, BPA-F&DOTA-Gd@LIPO-ANG effectively increased boron accumulation in glioma cells, inducing significant apoptosis and DNA damage upon neutron irradiation. Intravenously injected into orthotopic glioma model mice, BPA-F&DOTA-Gd@LIPO-ANG selectively accumulated in the tumor site, increasing tumor-to-normal tissue (T/N) and tumor-to-blood (T/B) ratios. Enhanced boron accumulation facilitated greater cytotoxic effects mediated by high-energy rays from the boron capture reaction, leading to significantly prolonged mice survival. In addition, in vitro and in vivo MRI validations confirmed its MRI visualization capability, meeting the demand for boron drug imaging for BNCT diagnosis and treatment integration. Overall, these results suggest that BPA-F&DOTA-Gd@LIPO-ANG is a promising targeted boron delivery system for MRI-guided BNCT in glioblastoma treatment.
研究领域:
纳米医学
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肿瘤学
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放射治疗学
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医学影像学
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药物递送
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神经肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TECHNOLOGY IN CANCER RESEARCH & TREATMENT
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2024
·
IF 2.7
Li-Hong Liu,Yu-Feng Liu,Hong-Bo Zhang,Xiao-Lei Liu,Han-Wen Zhang,Biao Huang,Fan Lin,Wei-Hua Li
PurposeDevelop an albumin nanoparticle-based nanoprobe for targeted glioblastoma (GBM) diagnosis and treatment, utilizing Angopep-2 for low-density lipoprotein receptor-related protein (LRP) targeting.MethodsCombined albumin-coated superparamagnetic iron oxide (SPIO), Carmustine (BCNU), and indocyanine green (ICG). Assessed morphology, size, Zeta potential, fluorescence, and drug encapsulation. Conducted in vitro fluorescence/MRI imaging and cell viability assays, and in vivo nanoprobe accumulation evaluation in brain tumors.ResultsANG-BSA/BCNU/ICG MNPs exhibited superior targeting and cytotoxicity against GBM cells in vitro. In vivo, enhanced brain tumor accumulation during imaging was observed.ConclusionThis targeted imaging and drug delivery system holds promise for efficient GBM therapy and intraoperative localization, addressing Blood-brain barrier (BBB) limitations with precise drug delivery and imaging capabilities.
研究领域:
纳米技术
·
神经肿瘤学
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药物递送系统
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医学成像
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）