International Journal of Nanomedicine
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2024
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IF 6.6
Zemin Ou,Yun You,Hong Yi,Xiaoqian Liu,Yan Tong,Dewen Liu,Jinyu Wang
Introduction Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra. The precise molecular mechanisms underlying neuronal loss in PD remain unknown, and there are currently no effective treatments for PD-associated neurodegeneration. Echinacoside (ECH) is known for its neuroprotective effects, which include scavenging cellular reactive oxygen species and promoting mitochondrial fusion. However, the blood-brain barrier (BBB) limits the bioavailability of ECH in the brain, posing a significant challenge to its use in PD treatment.Methods We synthesized and characterized PEGylated ECH liposomes (ECH@Lip) and peptide angiopep-2 (ANG) modified liposomes (ECH@ANG-Lip). The density of ANG in ANG-Lip was optimized using bEnd.3 cells. The brain-targeting ability of the liposomes was assessed in vitro using a transwell BBB model and in vivo using an imaging system and LC-MS. We evaluated the enhanced neuroprotective properties of this formulation in a the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model.Results The ECH@ANG-Lip demonstrated significantly higher whole-brain uptake compared to ECH@Lip and free ECH. Furthermore, ECH@ANG-Lip was more effective in mitigating MPTP-induced behavioral impairment, oxidative stress, dopamine depletion, and dopaminergic neuron death than both ECH@Lip and free ECH.Conclusion The formulation used in our study significantly enhanced the neuroprotective efficacy of ECH in the MPTP-induced PD model. Thus, ECH@ANG-Lip shows considerable potential for improving the bioavailability of ECH and providing neuroprotective effects in the brain.
研究领域:
神经科学
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药学
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生物技术
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DOI
PubMed
高影响因子
Nano Research
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2021
·Vol. 15
·期 2
·1455-1465
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IF 8.897
Wen Lijuan,Peng Yu,Wang Kai,Huang Zhihua,He Shiying,Xiong Ruiwen,Wu Longping,Zhang Fengtian,Hu Fuqiang
Glioblastoma (GBM) is one of the malignant brain tumors with high mortality and no curative treatments. Abnormally elevated vascular endothelial growth factor (VEGF) in GBM seriously disrupts the blood brain barrier (BBB) with an increased permeability, resulting in poor outcome and prognosis. RNAi interference has shown strong potential to inhibit VEGF expression, thus it is necessary to development an effective and safe gene delivery system possessing the ability to cross the BBB and target GBM cells. This study aims to explore the anti-GBM effect of angiopep-2 (Ap) peptide modified reactive oxygen species (ROS) cleavable thioketal (TK) linked glycolipid-like nanocarrier (CSTKSA) delivering anti-VEGF siRNA (R), termed as Ap-CSTKSA/R complexes. Ap functionalized modification produced an enhanced cellular uptake and a stronger bio-distribution of Ap-CSTKSA/R complexes in U87 MG cells and brain tumor tissues, respectively. Ap-CSTKSA/R complexes exhibited great superiority in GBM growth inhibition and finally translated into the longest survival period mainly via receptor-mediated targeting delivery, VEGF gene silencing accompanied with remarkable angiogenesis inhibition, and suppressed expression of caveolin-1 which is involved in BBB functional regulation in the occurrence and treatment of GBM. The study indicated that Ap functionalization on ROS-responsive glycolipid-like copolymer exhibits a promising and effective gene delivery platform for GBM targeted treatment.
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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基因治疗
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DOI
高影响因子
International Journal of Nanomedicine
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2024
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IF 6.6
Ming Li,Xinrui Zhang,Yujie Zhou,Yuteng Chu,Jie Shen,Yue Cai,Xuanrong Sun
Introduction Glioblastoma multiforme (GBM), a highly invasive and prognostically challenging brain cancer, poses a significant hurdle for current treatments due to the existence of the blood-brain barrier (BBB) and the difficulty to maintain an effective drug accumulation in deep GBM lesions.Methods We present a biomimetic nanoplatform with angiopep-2-modified macrophage membrane, loaded with indocyanine green (ICG) templated self-assembly of SN38 (AM-NP), facilitating active tumor targeting and effective blood-brain barrier penetration through specific ligand-receptor interaction.Results Upon accumulation at tumor sites, these nanoparticles achieved high drug concentrations. Subsequent combination of laser irradiation and release of chemotherapy agent SN38 induced a synergistic chemo-photothermal therapy. Compared to bare nanoparticles (NPs) lacking cell membrane encapsulation, AM-NPs significantly suppressed tumor growth, markedly enhanced survival rates, and exhibited excellent biocompatibility with minimal side effects.Conclusion This NIR-activatable biomimetic camouflaging macrophage membrane-based nanoparticles enhanced drug delivery targeting ability through modifications of macrophage membranes and specific ligands. It simultaneously achieved synergistic chemo-photothermal therapy, enhancing treatment effectiveness. Compared to traditional treatment modalities, it provided a precise, efficient, and synergistic method that might have contributed to advancements in glioblastoma therapy.
研究领域:
肿瘤学
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纳米技术
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药学
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生物医学工程
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2022
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IF 10.383
Caihua Ye,Meng Cheng,Lin Ma,Tianzhu Zhang,Zuhao Sun,Chunshui Yu,Junping Wang,Yan Dou
Prevention of Alzheimer’s disease (AD) is a global imperative, but reliable early interventions are currently lacking. Microglia-mediated chronic neuroinflammation is thought to occur in the early stage of AD and plays a critical role in AD pathogenesis. Here, oxytocin (OT)-loaded angiopep-2-modified chitosan nanogels (AOC NGs) were designed for early treatment of AD via inhibiting innate inflammatory response. Through the effective transcytosis of angiopep-2, AOC NGs were driven intravenously to cross the blood-brain barrier, enter the brain, and enrich in brain areas affected by AD. A large amount of OT was then released and specifically bound to the pathological upregulated OT receptor, thus effectively inhibiting microglial activation and reducing inflammatory cytokine levels through blocking the ERK/p38 MAPK and COX-2/iNOS NF-κB signaling pathways. Consecutive weekly intravenous administration of AOC NGs into 12-week-old young APP/PS1 mice, representing the early stage of AD, remarkably slowed the progression of Aβ deposition and neuronal apoptosis in the APP/PS1 mice as they aged and ultimately prevented cognitive impairment and delayed hippocampal atrophy. Together, the findings suggest that AOC NGs, which show good biosafety, can serve as a promising therapeutic candidate to combat neuroinflammation for early prevention of AD.
研究领域:
神经科学
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药理学
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神经炎症
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药物递送系统
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阿尔茨海默病研究
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DOI
PubMed
高影响因子
BIOMATERIALS
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2021
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IF 12.479
Lu Lu,Kui Wang,Chuanchuan Lin,Weihu Yang,Qiaojian Duan,Ke Li,Kaiyong Cai
The blood−brain barrier (BBB) is one of the major limitations of glioblastoma therapy in the clinic. Nanodrugs have shown great potential for glioblastoma therapy. Herein, we purposefully developed a multicomponent self-assembly nanocomplex with very high drug loading content for curing orthotopic glioblastoma with synergistic chemo-photothermal therapy. The nanocomplex consisted of self-assembled pH-responsive nanodrugs derived from amino acid-conjugated camptothecin (CPT) and canine dyes (IR783) coated with peptide Angiopep-2-conjugated copolymer of Ang-PEG-g-PLL. Specifically, the carrier-free nanocomplex exhibited a high drug loading content (up to 62%), good biocompatibility , and effective glioma accumulation ability. Moreover, the nanocomplex displayed good stability and pH-responsive behavior ex vivo . Both in vitro and in vivo results revealed that the nanocomplex could effectively cross the BBB and target glioma cells. Furthermore, the combination of chemotherapy and photothermal therapy of the nanocomplex achieved a better therapeutic effect, longer survival time, and minimized toxic side effects in orthotopic glioblastoma tumor-bearing nude mice . Overall, we modified the chemotherapeutic drug CPT so that it could self-assemble with other molecules into nanoparticles , which providing an alternative for the preparation of the carrier-free nanodrugs. The results highlighted the potential of self-assembly nanodrugs as a novel platform for effective glioblastoma therapy.
研究领域:
纳米技术
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药学
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癌症治疗
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生物医学工程
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神经科学
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DOI
PubMed
高影响因子
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