INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2018
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IF 3.862
Hongchen Hua,Xuemei Zhang,Hongjie Mu,Qingqing Meng,Ying Jiang,Yiyun Wang,Xiaoyan Lu,Aiping Wang,Sha Liu,Yaping Zhang,Zhihui Wan,Kaoxiang Sun
Gliomas are the most common malignant brain tumor, but treatment is limited by the blood–brain barrier (BBB), especially for chemotherapeutic drugs. Although some chemotherapy drugs can pass through the BBB, many of these agents are toxic to normal brain tissue. To maximize therapeutic effects, chemotherapeutic drugs must accumulate at the glioma site. In this study, a specific ligand (the RVG29 peptide) that can combine with acetylcholine receptors was conjugated to polyethylene glycol-modified poly-( d , l -lactide-co-glycolide) (PEG-PLGA) to develop a targeted carrier; preparation of the targeted docetaxel nanoparticles (DTX-NPs) was performed by the nanoprecipitation method. The NPs were approximately 110 nm and had smooth surfaces. Enzyme-linked immunoassay results showed that the amount of receptor on the surface of glioma cells was 2.04-fold higher than that of nonmalignant cells, which may promote accumulation of RVG29-modified NPs at the targeting site. NPs showed targeting properties for glioma cells compared with the non-targeting NPs in an in vitro cellular uptake test. Targeted NPs also showed better BBB penetration in an in vitro model. In vivo tests indicated that RVG29-PEG-PLGA-NPs could selectively accumulate in intracranial glioma tissue. In conclusion, these results indicated that the RVG29-modified NPs have potential efficacy for glioma therapy.
研究领域:
药学
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神经肿瘤学
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纳米技术
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DOI
PubMed
高影响因子
Nano Today
·
2024
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IF 13.2
Liting Chen,Chen Xu,Hainan Xu,Hongyu Liu,Zihan Ma,Jiahao Liu,Xiaoyu Gao,Wei Lv,Xinze Du,Xiao Zhao,Jing Shi,Keman Cheng,Funan Liu
Oncolytic virus therapy for brain tumors has achieved breakthrough progress in clinical applications, yet its potential is severely constrained by the mode of administration-direct intratumoral injection into the cranial cavity. Other administration routes face rapid clearance by neutralizing antibodies and obstacles posed by the blood-brain barrier. Herein, we engineered the oncolytic herpes simplex virus type 2 (OH2) with surface modifications of polyethylene glycol (PEG) and rabies virus glycoprotein 29 (RVG29, a BBB-penetrating peptide from the rabies virus), to form OH2-PEG-RVG. OH2-PEG-RVG could efficiently traversed the blood-brain barrier even in BALB/c mice with pre-existing anti-OH2 antibodies, leading to the accumulation of OH2 in the brain. More importantly, OH2-PEG-RVG maintained blood-brain barrier integrity without causing pathological changes or behavioral abnormalities in mice. Furthermore, OH2-PEG-RVG effectively inhibited brain tumor growth, transforming immunologically "cold" tumors into "hot" tumors, inducing a robust anti-tumor immune response, and prolonging the survival of the mice. These findings underscore the potential of OH2-PEG-RVG as a multifaceted therapeutic strategy for effective brain tumor treatment, offering insights into addressing blood-brain barrier limitations.
研究领域:
肿瘤学
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神经科学
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病毒学
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免疫疗法
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DOI
高影响因子
NEW JOURNAL OF CHEMISTRY
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2020
·Vol. 44
·期 15
·5692-5701
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IF 3.288
Hailing Han,Ying Zhang,Shunzi Jin,Ping Chen,Shi Liu,Zhigang Xie,Xiabin Jing,Zhanfeng Wang
Gliomas are the most common malignant brain tumors and notorious due to the blood–brain barrier (BBB). In this study, an RVG peptide is used as a targeting ligand to construct multi-targeting micelles (RVG–Dex–PTX) towards the brain (passing the BBB) and brain glioma. In vivo imaging and fluorescence imaging were carried out. The results showed that Cy5-labeled M(RVG, PTX) can cross the BBB and reach the intracranial C6 glioma, prolonging the median mean survival time. Specifically, the elevated RVG29 could enhance the uptake of the micelles by C6 glioma cells and thus enhance the PTX efficacy. In conclusion, RVG29 is a promising targeting peptide for the BBB and intracranial tumors, and the M(RVG, PTX) micelles prepared from dextran, PTX, and RVG29 are a potential formulation for C6 glioma treatment.
研究领域:
神经肿瘤学
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纳米医学
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药剂学
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癌症研究
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DOI
高影响因子
Bioengineering & Translational Medicine
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2022
·Vol. 7
·期 3
·e10395
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IF 10.684
Ruiyi Zhou,Lihong Zhu,Zhaohao Zeng,Rixin Luo,Jiawei Zhang,Rui Guo,Lei Zhang,Qunying Zhang,Wei Bi
Alzheimer's disease (AD) is an aging-related neurodegenerative disease. The main pathological features of AD are β-amyloid protein (Aβ) deposition and tau protein hyperphosphorylation. Currently, there are no effective drugs for the etiological treatment of AD. Rifampicin (RIF) is a semi-synthetic broad-spectrum antibiotic with anti-β-amyloid deposition, anti-inflammatory, anti-apoptosis, and neuroprotective effects, but its application in AD treatment has been limited for its strong hydrophobicity, high toxicity, short half-life, low bioavailability, and blood–brain barrier hindrance. We designed a novel brain-targeted and MRI-characteristic nanomedicine via loading rabies virus protein 29 (RVG29), rifampicin, and Gd on poly ( l -lactide) nanoparticles (RIF@PLA-PEG-Gd/Mal-RVG29). The cytotoxicity assay demonstrated that RIF@PLA-PEG-Gd/Mal-RVG29 had favorable biocompatibility and security. Fluorescence imaging in vivo showed that PLA-PEG-Gd/Mal-RVG29 could deliver rifampicin into the brain by enhancing cellular uptake and brain targeting performance, leading to improvement of the bioavailability of rifampicin. In in vivo study, RIF@PLA-PEG-Gd/Mal-RVG29 improved the spatial learning and memory capability of APP/PS1 mice in the Morris water maze, as compared to rifampicin. Immunofluorescence, TEM, immunoblotting, and H&E staining revealed that RIF@PLA-PEG-Gd/Mal-RVG29 reduced Aβ deposition in hippocampal and cortex of APP/PS1 mice, improved the damage of synaptic ultrastructure, increased the expression level of PSD95 and SYP, as well as reduced the necrosis of neurons. These findings suggest that RIF@PLA-PEG-Gd/Mal-RVG29 may be an effective strategy for the treatment of AD.
研究领域:
神经科学
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药学
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纳米技术
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药物递送系统
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DOI
PubMed
高影响因子
ACS Applied Nano Materials
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2026
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IF 5.8
Chunlian Liu,Siwen Wang,Haifan Yu,Kai Duo,Chunyu Wang,Jing Jiang,Lin Li
Parkinson’s disease (PD), the second leading cause of neurodegenerative disease worldwide, severely impairs the quality of life for the elderly. While current clinical treatments can alleviate symptoms, they fail to halt the progressive death of neurons, making the disease progression irreversible. This treatment bottleneck is largely attributed to the inability to effectively alleviate the “energy metabolism crisis” of dopaminergic neurons. Against this backdrop, piperine (Pip) has shown some neuroprotective potential, but its poor water solubility and inability to penetrate the blood–brain barrier (BBB) limit its application. This study aimed to develop RVG29 peptide-modified erythrocyte membrane biomimetic nanoparticles (RVG29-RM@Pip NPs) to address delivery challenges and explore metabolic intervention strategies. This system uses PLGA to load piperine, achieving immune escape and active brain targeting through biomimetic camouflage and RVG29 guidance. In vitro and in vivo experiments confirmed that these nanoparticles can efficiently penetrate the BBB, restore mitochondrial membrane potential, scavenge reactive oxygen species, and significantly improve motor dysfunction and neuronal loss in MPTP mice. Mechanistically, it remodels neuronal glycolysis and respiratory chain function by synergistically upregulating GLUT1, the rate-limiting enzyme PGK1, and mitochondrial complex I, restoring energy homeostasis and inhibiting apoptosis. This study not only constructed a brain-targeted delivery system but also revealed a mechanism and candidate approach for treating PD through metabolic remodeling.
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高影响因子
International Journal of Nanomedicine
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2024
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IF 6.6
Yi Liang,Liping Feng,Yue Zheng,Yunzhen Gao,Rongying Shi,Zhirong Zhang,Xue Ying,Yingchun Zeng
Introduction Parkinson’s disease (PD) is a multifactor-induced neurodegenerative disease with high incidence in the elderly population. We found for the first time that the combination of dopamine (DA) and 3-n-butylphthalide (NBP) has great potential for the synergistic treatment of PD. To further improve the therapeutic performance of the drugs, a brain-targeting liposomal co-delivery system encapsulating NBP and DA ((NBP+DA)-Lips-RVG29) was designed using a rabies virus polypeptide with 29 amino acids (RVG29) as the targeting ligand.Methods The synergistic neuroprotective effects of NBP and DA were assessed in 6-OHDA-induced PC12 cells. Then, (NBP+DA)-Lips-RVG29 loading with NBP and DA at an optimal ratio was prepared using the thin-film hydration and sonication method. The physicochemical and biological characterization of (NBP+DA)-Lips-RVG29 were systemically investigated, and the therapeutic efficiency and underlying mechanisms of (NBP+DA)-Lips-RVG29 were also explored in vitro and in vivo. Finally, the safety of (NBP+DA)-Lips-RVG29 was evaluated.Results The synergistic effects of NBP and DA peaked at 1:1 (NBP/DA, mol/mol). The functionalized liposomes showed significantly higher uptake efficiency and blood-brain barrier (BBB) penetration efficiency in vitro. After systemic administration, (NBP+DA)-Lips-RVG29 prolonged the blood circulation of drugs, enhanced BBB penetration and increased drug accumulation in the striatum, substantia nigra and hippocampus. Moreover, (NBP+DA)-Lips-RVG29 showed excellent neuroprotective effects in a cellular PD model of PC12 cells and improved therapeutic efficacy in a PD mouse model. Furthermore, the safety evaluation of (NBP+DA)-Lips-RVG29 revealed no systemic toxicity.Conclusion NBP and DA exhibited the synergistic anti-PD effects. The RVG29-modified liposomes encapsulating NBP and DA contributed to the accumulation of drugs in the brain lesions area of PD and further improved treatment efficacy. Therefore, (NBP+DA)-Lips-RVG29 represents a promising strategy for the treatment of PD and other neurodegenerative diseases.
研究领域:
神经科学
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药理学
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药物递送系统
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神经退行性疾病
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产品关联
DOI
PubMed
高影响因子
Materials Today Nano
·
2023
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IF 10.3
Dong Zhang,Jianglong Kong,Xueying Huang,Jie Zeng,Qiaohui Du,Tao Yang,Hui Yue,Qing Bao,Yao Miao,Yajing Xu,Honglin Jiang,Fang Lei,Mingying Yang,Yi Wang,Chuanbin Mao
Targeted brain tumor therapy by nanoparticles (NPs) remains a daunting challenge due to the difficulty for NPs to go through the blood-brain barriers (BBB) and blood-brain tumor barriers (BBTB). In addition, Dactolisib (Dac) is an effective dual PI3K/mTOR inhibitor for cancer treatment. It was the first PI3K inhibitor to enter clinical trials but exhibited toxicity to normal tissues if not delivered to tumor sites by a tumor-targeting carrier. To explore Dac for glioblastoma (GBM) therapy while avoiding its toxicity, we developed a new brain tumor-targeting drug delivery system self-assembled from zein, a cell membrane-penetrating amphiphilic protein originally present in corn. Specifically, the amphiphilicity of zein drove it to self-assemble into NPs that encapsulated Dac with high efficiency. RVG29, a 29-mer brain-targeting peptide, was chemically conjugated to zein constituting the NPs, forming Dac-encapsulated NPs (zein-RVG-Dac_NPs). In vitro assays were conducted to verify the capability of the NPs in penetrating BBB/BBTB, targeting GBM cancer cells and killing them. ELISA was employed to assess the expression of nicotinic acetylcholine receptors (nAChR) on the cancer cells to understand the mechanism of cancer cell membrane penetration by the NPs. The NPs were intravenously injected into orthotopic GBM mice models to demonstrate the brain tumor targeting as well as the effective GBM therapy due to the targeted delivery of Dac to brain tumors. The treated tumors were immunohistochemically analyzed to verify the tumor destruction. To confirm the biosafety of the NPs in treating GBM, we also histopathologically evaluated the major normal organs and chemically analyzed the blood biomarkers. We found that a combination of zein and RVG29 facilitated the zein-RVG-Dac_NPs to cross the BBB/BBTB and became uptaken by the GBM cells through the nAChR-mediated pathways, enabling the NPs to cross BBB/BBTB and deliver Dac selectively to GBM cells. Hence, administration of the NPs through tail veins significantly increased the accumulation of Dac in the orthotopic brain tumor of mice and effectively inhibited tumor growth. Neither toxicity nor adverse effects in the major organs were found due to the excellent biocompatibility of zein and the targeted delivery of Dac into brain tumor cells. Hence, integrating a cancer cell-penetrating natural protein (zein) and a brain-targeting peptide (RVG29) can form NPs that can effectively penetrate BBB/BBTB and then enter brain tumor cells to release Dac, leading to highly effective targeted brain cancer therapy. Such NPs can be extended to the development of therapeutics for treating different brain diseases due to their unique combination of biocompatibility and brain-targeting capability.
研究领域:
神经科学
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药学
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癌症研究
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纳米技术
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药物递送系统
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产品关联
DOI
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2024
·Vol. 22
·期 1
·1-19
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IF 10.6
Zhang Liding,Cao Kai,Xie Jun,Liang Xiaohan,Gong Hui,Luo Qingming,Luo Haiming
Amyloid-β (Aβ) readily misfolds into neurotoxic aggregates, generating high levels of reactive oxygen species (ROS), leading to progressive oxidative damage and ultimately cell death. Therefore, simultaneous inhibition of Aβ aggregation and scavenging of ROS may be a promising therapeutic strategy to alleviate Alzheimer’s disease pathology. Based on the previously developed antibody 1F12 that targets all forms of Aβ 42 , we developed an Aβ 42 and ROS dual-targeting nanocomposite using biodegradable mesoporous silica nanoparticles as carriers to load ultra-small cerium oxide nanocrystals (bMSNs@Ce-1F12). By modifying the brain-targeted rabies virus glycoprotein 29 (RVG29-bMSNs@Ce-1F12), this intelligent nanocomposite can efficiently target brain Aβ-rich regions. Combined with peripheral and central nervous system treatments, RVG29-bMSNs@Ce-1F12 can significantly alleviate AD symptoms by inhibiting Aβ 42 misfolding, accelerating Aβ 42 clearance, and scavenging ROS. Furthermore, this synergistic effect of ROS scavenging and Aβ clearance exhibited by this Aβ 42 and ROS dual-targeted strategy also reduced the burden of hyperphosphorylated tau, alleviated glial cell activation, and ultimately improved cognitive function in APP/PS1 mice. Our findings indicate that RVG29-bMSNs@Ce-1F12 is a promising nanodrug that can facilitate multi-target treatment of AD.
研究领域:
神经科学
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纳米技术
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药学
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分子生物学
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治疗学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）