COLLOIDS AND SURFACES B-BIOINTERFACES
·
2023
·
IF 5.8
Wenbo Wang,Shihao Zhou,Zhaoyi Cheng,Dong Ma,Tao Liu
CRISPR-Cas9 technology has been proven to be the most straightforward and accurate tool for gene therapy, but some limitations, such as the inefficient transfection or inability to precisely target, prevent the gene therapy from achieving the desired therapeutic effect. To overcome these, a kind of glutathione-sensitive cationic vectors, hyperbranched polyamide amine (HPAA) was designed for Delivery of CRISPR-Cas9 RNA plasmid, and the cyclic RGD (Arg-Gly-Asp) was conjugated for the targeted treatment of nasopharyngeal carcinoma (NPC). Disulfide bonds in HPAA segments can specifically respond to the high glutathione concentration in the tumor microenvironment. Meanwhile, RGD could especially interact to the integrin α v β 3 receptors which are highly expressed on the surface of NPC tumor cells. The results showed that more HPAA-RGD/SGK3-gRNA complexes could be uptaken by NPC HNE-1 cells after RGD was conjugated, and then the plasmid could be accumulated in the NPC tumor as well, which may assure the satisfied NPC therapy effect in vivo. In transfection assays, this complex showed the acceptable gene transfection efficiency in vitro and the obvious tumor inhibition effect in vivo, suggested a potential application in gene therapy to NPC.
研究领域:
分子生物学
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基因治疗
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癌症研究
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHYSICAL CHEMISTRY B
·
2025
·
IF 2.9
Shengzong Lan,Liuyang Dong,Tianfu Zhang,Peilun Shen,Dianwen Liu,Zhengchang Shen
In this research, 2-hydroxy phosphonyl acetic acid (HPAA) was employed as an environmentally friendly inhibitor to facilitate the flotation separation of apatite from dolomite. The results of the microflotation test indicated that 15 mg/L HPAA reduced the recovery of dolomite from 82.55% to 21.07%, while the recovery of apatite remained at 79.81%. The flotation test of artificial mixed ore showed that after adding HPAA, the grade of P2O5 in the mixed concentrate increased from 19.96% to 26.67%, and the recovery reached 75.88%. Adding Na3PO4·12H2O to the slurry effectively mitigated the influence of interfering ions on the flotation separation of apatite from dolomite. The scanning results of atomic force microscopy showed that the adsorption density and adsorption height of HPAA on the surface of dolomite were both stronger than those on the surface of apatite. The results of X-ray photoelectron spectroscopy showed that HPAA reacted with the Ca and Mg sites on the surface of dolomite. Time-of-flight secondary ion mass spectrometry detected characteristic ion fragments of C2O6PCaMg+ on the surface of dolomite treated with HPAA, and the ion fragment intensifications of C2O6PCaH+ and C2O6PMgH+ were significantly enhanced. The calculation results of density functional theory showed that the configuration of HPAA is the most stable when it simultaneously adsorbs Ca and Mg ion sites on the surface of dolomite. There is electron transfer between O in the HPAA structure and Ca and Mg ions on the mineral surface, indicating that a chemical reaction has occurred between them. This research provides a theoretical basis for the design and development of green flotation inhibitors for phosphate rock.
研究领域:
矿物加工
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表面化学
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环境化学
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材料科学
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化学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Medical Sciences
·
2024
·Vol. 21
·期 15
·3018
·
IF 3.2
Qi Zhang,Chao Hu,Baoqing Qu,Cuiping Zhang,Longtao He
This work aimed to demonstrate the therapeutic effects of tumor microenvironment-responsive nanotherapeutic drugs targeting PSD95/Discs-large/ZO-1 domain (PDZ)-binding-kinase (PBK) in medulloblastoma Daoy and ONS-76 cells. The objective was to provide critical theoretical and practical foundations for the clinical adoption of tumor microenvironment-responsive nanotherapeutic drugs targeting PBK. The rabies virus glycoprotein (RVG) was utilized as a specific targeting molecule to form a tumor microenvironment-responsive nanocomplex, HPAA/RVG/PBK-siRNA, which incorporated glutathione (GSH) as a microenvironment stimulus factor within a hyperbranched polymer polyamide amine (HPAA). This nanocomplex also carried PBK-small interfering RNA (siRNA) for targeted PBK therapy. Characterization of HPAA, maleimide-polyethylene glycol-N-succinyl ester (MAL-PEG-NHS), HPAA-PEG, RVG, HPAA-RVG, and HPAA/RVG/PBK-siRNA was conducted using nuclear magnetic resonance spectroscopy, high-performance liquid chromatography (HPLC), dynamic light scattering, and transmission electron microscopy (TEM). Flow cytometry was employed to assess endocytosis and cell transfection of HPAA-RVG and HPAA/RVG/PBK-siRNA in Daoy and ONS-76 cells. The two cell lines were treated with HPAA/RVG/PBK-siRNA (HPAA/siRNA group), methoxy-PEG polyethylenimine (PEI-25k)/PBK-siRNA (PEI group), HPAA/RVG nanocarriers without PBK-siRNA (HPAA/RVG group), Dharmacon™ non-targeting siRNA (shNTC group), PBK-siRNA (Control group 1), AChR inhibitor (Control group 2), and GSH inhibitor (Control group 3), and compared with the control group (medium without any substances). Western blot analysis validated PBK expression levels (ELs) in various cell groups. Additionally, cell viability and proliferation were evaluated using methyl tetrazolium (MTT) assays and 5-Bromo-2'-deoxyuridine (BrdU) incorporation assays. The results revealed proton absorption peaks for HPAA at 2.78 ppm, 3.21 ppm, and 3.49 ppm, while RVG and HPAA-RVG exhibited characteristic absorption peaks at 23.653 min and 23.584 min, respectively, with peak areas of 4,856.6 and 6,927.3 for RVG. The nanoparticle sizes were 50-100 nm for HPAA-RVG and 100 nm for HPAA/RVG/PBK-siRNA, displaying spherical morphology and uniform size distribution. The average potential of HPAA-PEG was lower than that of HPAA ( P <0.05), and HPAA-RVG showed dramatically lower potential than HPAA ( P <0.001). At 8 hours, Daoy cells displayed higher endocytosis rates versus ONS-76 cells ( P <0.05). The transfection rates of HPAA-RVG in both ONS-76 and Daoy cells were higher than those of HPAA, with Daoy cells showing higher transfection rates than HPAA ( P <0.05). Under HPAA-RVG treatment, AChR levels in ONS-76 cells were significantly lower than those in Daoy cells ( P < 0.05). Compared to the control group, the PBK protein expression levels, cell survival rates, and the number of cells in the proliferative phase were significantly reduced in Control group 1, the PEI group, and the HPAA/siRNA group in both ONS-76 and Daoy cells, with the ONS-76 cells in the HPAA/siRNA group showing the lowest values among these groups ( P < 0.05). In summary, the findings indicated that the tumor microenvironment-responsive nanocomposite HPAA/RVG/PBK-siRNA selectively inhibited PBK expression in Daoy medulloblastoma cells, showcasing potential applicability in medulloblastoma therapy.
研究领域:
肿瘤学
·
药学
·
分子生物学
·
纳米技术
✓ 已验证
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）