PARTICLE & PARTICLE SYSTEMS CHARACTERIZATION
·
2018
·Vol. 35
·期 6
·1800011
·
IF 4.384
Haidi Guan,Liucan Wang,Jixi Zhang,Yuxin Xing,Kaiyong Cai
Small particle size and strong host–guest interactions are prerequisites in the field of nuclear-targeting nanocarriers for overcoming the multidrug resistance of cancer cells. A novel scheme of synthesizing hybrid organic–inorganic nanocarriers with mesopores is introduced to enhance the delivery efficiency of therapeutic drugs. Specifically, inorganic silica and organic polydopamine (PDA) are integrated inside the pore framework by the assistance of organic silanes terminated by amino/thiol groups. Silica-etching by hydrothermal treatment leads to the selective enrichment of bioadhesive PDA and size reductions for the hybrids (to ≈30 nm). Interestingly, a high drug loading capacity (523 µg mg −1 for doxorubicin hydrochloride), as well as pH/ glutathione dual-responsive drug release properties, are realized by the nanocarriers, owing to their high surface area (825 m 2 g −1 ) and the π-stacking and/or hydrophobic–hydrophobic interactions stemming from PDA. More importantly, the conjugation of TAT peptide facilitates the intranuclear localization of the nanocarriers and the release of the encapsulated drugs directly within the nucleoplasm of the multidrug resistant MCF-7/ADR cancer cells. Therefore, these results provide a controllable method of engineering high-surface-area nanocarriers with bioadhesive polymers on the pore surface for advanced drug delivery applications.
研究领域:
纳米医学
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癌症治疗
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药物递送系统
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材料科学
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生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
International Journal of Nanomedicine
·
2023
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IF 8
Lu Lu,Hongyuan Chen,Longkun Wang,Lin Zhao,Yanna Cheng,Aijun Wang,Fengshan Wang,Xinke Zhang
Purpose Vascular endothelial growth factor receptor 2 (VEGFR-2) and neuropilin-1 (NRP-1) are two prominent synergistic receptors overexpressed on new blood vessels in glioma and may be promising targets for antiglioma therapy. The aim of this study was to design a dual receptor targeting and blood-brain barrier (BBB) penetrating peptide-modified polyethyleneimine (PEI) nanocomplex that can efficiently deliver the angiogenesis-inhibiting secretory endostatin gene (pVAXI-En) to treat glioma.Materials and Methods We first constructed the tandem peptide TAT-AT7 by conjugating AT7 to TAT and evaluated its binding affinity to VEGFR-2 and NRP-1, vasculature-targeting ability and BBB crossing capacity. Then, TAT-AT7-modified PEI polymer (PPTA) was synthesized, and a pVAXI-En-loaded PPTA nanocomplex (PPTA/pVAXI-En) was prepared. The physicochemical properties, cytotoxicity, transfection efficiency, capacities to cross the BBB and BTB (blood-tumor barrier) and glioma-targeting properties of PPTA/pVAXI-En were investigated. Moreover, the in vivo anti-angiogenic behaviors and anti-glioma effects of PPTA/pVAXI-En were evaluated in nude mice.Results The binding affinity of TAT-AT7 to VEGFR-2 and NRP-1 was approximately 3 to 10 times greater than that of AT7 or TAT. The cellular uptake of TAT-AT7 in endothelial cells was 5-fold and 119-fold greater than that of TAT and AT7 alone, respectively. TAT-AT7 also displayed remarkable efficiency in penetrating the BBB and glioma tissue in vivo. PPTA/pVAXI-En exhibited lower cytotoxicity, stronger BBB and BTB traversing abilities, higher selective glioma targeting and better gene transfection efficiency than PEI/pVAXI-En. More importantly, PPTA/pVAXI-En significantly suppressed the tube formation and migration of endothelial cells, inhibited glioma growth, and reduced the microvasculature in orthotopic U87 glioma-bearing nude mice.Conclusion Our study demonstrates that PPTA/pVAXI-En can be exploited as an efficient dual-targeting nanocomplex to cross the BBB and BTB, and hence it represents a feasible and promising nonviral gene delivery system for effective glioma therapy.
研究领域:
癌症治疗
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药学
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分子生物学
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神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2017
·Vol. 7
·期 34
·20766-20778
·
IF 3.108
Nan Wang,Xin Jin,Xinyuan Zhu
The effective treatments for central nervous system (CNS) diseases are impeded mostly by the existence of the blood–brain barrier (BBB). The accumulation of therapeutic drugs inside the brain is far from the therapy threshold, which is closely related to the transient circulation time of drugs and their carriers. Herein, a core–shell protein-based long-circulation delivery platform was constructed. Through in situ free radical polymerization, a zwitterionic polymer poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) was modified on the surface to prolong the circulation lifetime with a biomimetic structure induced by a phosphorylcholine (PC) head-group similar to the lipids in the outer membrane of living cells. A cell-penetrating peptide, HIV-1 trans-activating transcriptor (TAT) was conjugated on the surface of the protein-based nanoparticles, endowing the delivery platform with BBB-crossing ability. The BBB-permeability of the nanoparticles was investigated both in vitro and in vivo. Encapsulated with zwitterionic polymer PMPC, the nanoparticles showed a long circulation lifetime due to strong resistance to nonspecific adsorption and provided a better chance for BBB penetration. The delivery platform had enhanced permeability for BBB and a longer retention time inside the brain in a healthy mouse model. Overall, the surface modification with zwitterionic polymer PMPC and cell-penetrating peptide TAT changes the circulation modality of the nanoparticles in vivo, and provides a promising pathway for BBB crossing as a potential drug delivery platform for CNS related disease therapy.
研究领域:
药学
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纳米技术
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神经科学
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药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Chang Liu,Qi Yan,Xuying Ding,Meijun Zhao,Chen Chen,Qian Zheng,Huiying Yang,Yining Xie
Brain-derived neurotrophic factor (BDNF) is a neurotrophic protein that promotes neuronal survival, increases neurotransmitter synthesis, and has potential therapeutic effects in neurodegenerative and psychiatric diseases, but its drug development has been limited by the fact that recombinant proteins of BDNF are unstable and do not penetrate the blood-brain barrier (BBB). In this study, we fused a TAT membrane-penetrating peptide with BDNF to express a recombinant protein (TBDNF), which was then PEG-modified to P-TBDNF. Protein characterization showed that P-TBDNF significantly improved the stability of the recombinant protein and possessed the ability to penetrate the BBB, and in cellular experiments, P-TBDNF prevented MPTP-induced nerve cell oxidative stress damage, apoptosis and inflammatory response, and its mechanism of action was closely related to the activation of tyrosine kinase B (TrkB) receptor and inhibition of microglia activation. In animal experiments, P-TBDNF improved motor and cognitive deficits in MPTP mice and inhibited pathological changes in Parkinson's disease (PD). In conclusion, this paper is expected to reveal the mechanism of action of P-TBDNF in inhibiting neurotoxicity, provide a new way for treating PD, and lay the foundation for the future development of recombinant P-TBDNF.
研究领域:
神经科学
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药理学
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分子生物学
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神经退行性疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
GIANT
·
2020
·
IF 0
Wenbo Zhang,Zihe Zhai,Shenyu Huang,Zhengwei Mao,Yixian Zhang,Changyou Gao
The delivery of nanomaterials or therapeutics into cells takes a decisive role for their applications in nanomedicine. Nature's creations such as viruses provide valued inspiration for design of nano-architectures in cellular delivery. We report herein the fabrication of biodegradable and biocompatible nanoparticles (NPs) with viral-mimicking morphology and constituents as a nanoplatform, which has rarely been reported to the best of our knowledge, for promoting cellular uptake and achieving high therapeutic efficiency in vivo . The chitosan-porphyrin-based NPs were endowed with a viral-imitating morphology through a novel pH-responsive decomposition-induced self-assembly method. By successive conjugation of Tat peptides and modification of lipids, morphological and constituent viral-mimicking NPs were obtained. Compared with the counterpart of non-viral-mimicking NPs, the viral-mimicking NPs showed prominent superiority in enhancing cell internalization (10 times higher). Loading of near-infrared photosensitizer– indocyanine green into these NPs demonstrated the striking capability of the viral-mimicking nanoparticles in therapeautic delivery and photothermal anti-tumor effect in vitro and in vivo . This concept and strategy provides an enlightening methodology on the design and fabrication of therapeutic delivery systems, which is significant for nanobiotechnology.
研究领域:
纳米医学
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癌症治疗
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生物材料
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药物递送系统
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生物医学工程
✓ 已验证
产品关联
DOI
Nanoscale
·
2020
·Vol. 12
·期 9
·5380-5396
·
IF 6.895
Yalin Sun,Yan Liang,Na Hao,Xiaoheng Fu,Bin He,Shangcong Han,Jie Cao,Qingming Ma,Wen Xu,Yong Sun
9-Nitro-20(S)-camptothecin (9-NC) is a broad-spectrum antitumor drug used in tumor treatments, but its clinical applications and antitumor efficacy are limited by its structural instability, poor solubility, and extremely low drug utilization in tumor tissues. In this study, enzyme-sensitive nuclear-targeted dual-functional polymeric micelles were developed for 9-NC delivery with a high drug loading content (12.93 ± 0.88%), steady-state circulation, and a rapid attack at the “heart” of tumor cells. Briefly, chrysin (CHR) as a π-conjugated moiety was immobilized on the PCL terminal in the TAT–PCL amphiphiles and combined with the ALAL peptide as a linker on HA chains to yield the ultimate CHR–PCL–TAT–ALAL–HA (HATPC) amphiphiles. Spherical 9-NC-loaded micelles were obtained from the self-assembly of the dual-functional amphiphiles comprising HATPC and 9-NC with uniform nanosize (121.6 ± 5.79 nm), well-distributed morphology (PDI: 0.256), and negative surface charge (−23.2 ± 0.5 mV), yielding high stability during blood circulation. In this drug delivery system, HA acts as an active tumor-targeting instrument via CD44-receptor-mediated endocytosis; further, the ALAL peptide could be cutoff in the lysosomes of the tumor cells due to the high expression of cathepsin B, leading to lysosomal escape, while the secondary polymeric micelles targeted the tumor cell nucleus via the exposed TAT peptide. The enzyme sensitivity and nuclei targetability of the 9-NC/HATPC micelles were confirmed by dynamic light scattering and confocal laser scanning microscopy analyses. As compared to free 9-NC and traditional mPEG2k–PCL2k polymeric micelles, 9-NC/HATPC micelles were the most concentrated in the tumor cell nucleus; therefore, they exhibited the highest cytotoxicity against SKOV3 tumor cells both in vitro (IC50 = 0.03 μg mL−1) and in vivo. This enzyme-sensitive nuclear-targeted dual-functional drug delivery system involving HATPC provided a new and promising strategy for enhanced 9-NC delivery and antitumor efficacy.
研究领域:
药学
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纳米技术
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癌症研究
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Biological Sciences
·
2024
·
IF 8.2
Jianzhi Wu,Liping Gong,Yijie Li,Tiegang Liu,Rong Sun,Kexin Jia,Runping Liu,Fei Dong,Xiaohong Gu,Xiaojiaoyang Li
Idiopathic pulmonary fibrosis (IPF) is characterized by fibrotic matrix deposition and irreversible aberrant tissue remodeling. Their mechanisms of action are associated with the activation of macrophages and a disturbed immune environment. We aim to determine how these activated macrophages influenced the pathogenesis of pulmonary fibrosis. We found the fibrotic areas of IPF patients contained more serum and glucocorticoid-induced kinase 1 (SGK1)-positive and M2-type macrophages. Similarly, bleomycin (BLM)+LPS significantly triggered high expression of SGK1 in the IPF mice, accompanied by destroyed lung structure and function, increased fibrosis markers and disturbed immune microenvironment. Mechanistically, SGK1 markedly promoted the reprogramming of M2-type macrophages in fibrotic lungs by triggering glycogen synthase kinase 3beta (GSK3β)-tat-interacting protein 60 (TIP60)- histone-3 lysine-27 acetylation (H3K27ac) signalings, which further released chemokine (C-C motif) ligand 9 (CCL9) to attract Th17 cells and delivered TGF-β to fibroblasts for synergistically destroying immune microenvironment, which was largely reversed by macrophage depletion in mice. We took macrophages as the entry point to deeply analyze IPF pathogenesis and further provided insights for the development of novel drugs represented by SGK1.
研究领域:
肺科学
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免疫学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2020
·
IF 8.758
Zhenqiang Fan,Zongqiong Lin,Zepeng Wang,Jianfeng Wang,Minhao Xie,Jianfeng Zhao,Kai Zhang,Wei Huang
In this work, we fabricated a dual-wavelength electrochemiluminescence ratiometric biosensor based on electrochemiluminescent resonance energy transfer (ECL-RET). In this biosensor, Au nanoparticle-loaded graphitic phase carbon nitride (Au-g-C3N4) as a donor and Au-modified dimethylthiodiaminoterephthalate (TAT) analogue (Au@TAT) as an acceptor were investigated for the first time. Besides, tetrahedron DNA probe was immobilized onto Au-g-C3N4 to improve the binding efficiency of the transcription factor and ECL ratiometric changes on the basis of the ratio of ECL intensities at 595 and 460 nm, which were obtained through the formation of a sandwich structure of DNA probe–antigen–antibody. Our biosensor achieved the assay of NF-κB p50 with a detection limit of 5.8 pM as well as high stability and specificity.
研究领域:
分析化学
·
生物传感器
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电化学
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纳米技术
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）