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相关概念视频

The Nernst Equation02:59

The Nernst Equation

Nonstandard Reaction Conditions
The interconnection between standard cell potentials and various thermodynamic parameters such as the standard free energy change ΔG° and equilibrium constant K has been previously explored. For example, a redox reaction involving zinc(II) and tin(II) ions at 1 M concentration with Eºcell = +0.291 V and ΔG° = −56.2 kJ is spontaneous.
Nuclear Stability03:18

Nuclear Stability

Protons and neutrons, collectively called nucleons, are packed together tightly in a nucleus. With a radius of about 10−15 meters, a nucleus is quite small compared to the radius of the entire atom, which is about 10−10 meters. Nuclei are extremely dense compared to bulk matter, averaging 1.8 × 1014 grams per cubic centimeter. If the earth’s density were equal to the average nuclear density, the earth’s radius would be only about 200 meters.
To hold positively charged protons together in the...
Atomic Nuclei: Nuclear Relaxation Processes01:23

Atomic Nuclei: Nuclear Relaxation Processes

In the absence of an external magnetic field, nuclear spin states are degenerate and randomly oriented. When a magnetic field is applied, the spins begin to precess and orient themselves along (lower energy) or against (higher energy) the direction of the field. At equilibrium, a slight excess population of spins exists in the lower energy state. Because the direction of the magnetic field is fixed as the z-axis,  the precessing magnetic moments are randomly oriented around the z-axis. This...
Nuclear Overhauser Enhancement (NOE)01:06

Nuclear Overhauser Enhancement (NOE)

Irradiation of a spin-active nucleus causes an increase or decrease in the signal intensity of neighboring nuclei that are not necessarily chemically bonded or involved in J-coupling. This phenomenon, called the nuclear Overhauser enhancement (NOE), results from through-space interactions between the nuclear spins. The NOE effect decreases with increasing internuclear distance and is generally not observed beyond 4 angstroms. In NOE, dipole-dipole interactions between neighboring spin-active...
Insensitive Nuclei Enhanced by Polarization Transfer (INEPT)01:15

Insensitive Nuclei Enhanced by Polarization Transfer (INEPT)

Insensitive Nuclei Enhanced by Polarization Transfer (INEPT) is an advanced Nuclear Magnetic Resonance (NMR) technique specifically designed to detect and enhance the signals of low-abundance nuclei, such as carbon-13 and nitrogen-15, in small molecules. The fundamental principle behind INEPT is the transfer of polarization from a more abundant and highly polarizable nucleus, typically hydrogen-1, to the low-abundance nucleus of interest. This process effectively boosts the NMR signal of the...
Electrochemical Systems01:24

Electrochemical Systems

Electrochemical systems provide a fascinating insight into the dynamic interplay of charged species within various phases. One notable example is the interaction between a membrane permeable to K⁺ ions but not to Cl⁻ ions, separating an aqueous KCl solution from pure water. As K⁺ ions diffuse through the membrane, they generate net charges on each phase, leading to a potential difference between them.Similarly, when a piece of Zn is immersed in an aqueous ZnSO₄ solution, the Zn metal, composed...

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通过稳定的阴离子-德克斯三元系统提升核酸输送.

Alex Cheng1, Ying Liu1, Hai-Qing Song1,2

  • 1Department of Chemical Engineering, University of Illinois at Chicago, Chicago, Illinois 60607.

Biointerphases
|October 4, 2023
PubMed
概括

研究人员开发了一种新的离子接种的德克斯涂层,以改善基因治疗的化聚合物/核酸复合物. 这种新的涂层增强了血液的稳定性和转染效率,为提供核酸治疗提供了一个有前途的解决方案.

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科学领域:

  • 生物材料科学 生物材料科学
  • 基因疗法交付 基因疗法交付
  • 纳米技术纳米技术

背景情况:

  • 核酸疗法为难以治疗的疾病提供了潜力,但需要有效的传递载体.
  • 阴离子聚合物是有效的,但易于蛋白质聚合,由于正电荷,减少了转染.
  • 开发稳定高效的输送系统仍然是基因疗法的关键挑战.

研究的目的:

  • 设计和合成离子移植的德克斯 (Dex-LipE5H) 作为聚合物/核酸复合物的可交叉链接涂层.
  • 评估新型三元传递系统 (CDex-LipE5H/PEI/核酸) 的稳定性,细胞毒性和传染效率.
  • 为了证明系统在挑战细胞系和基因淘汰应用中的有效性.

主要方法:

  • 通过迈克尔的添加反应将阴性 (LipE5H) 接种到通过二维尼尔硫修饰的上,以产生Dex-LipE5H.
  • 构建了一个三元核酸输送系统,CDex-LipE5H/PEI/核酸.
  • 评估了细胞毒性,抗蛋白吸收和HepG2细胞的传染效率 (包括高血清条件).
  • 使用PCSK9基因淘汰试验验证了siRNA干扰的有效性.

主要成果:

  • 合成的Dex-LipE5H有效地作为可交叉链接的涂层,增强了化聚合物/核酸复合物的稳定性.
  • 与PEI/pDNA和Dex-LipE5H/PEI/pDNA相比,三元系统 (CDex-LipE5H/PEI/核酸) 的细胞毒性较低,抗蛋白吸收能力更强.
  • 在HepG2细胞中,即使在20%的血清介质中,也实现了显著的传染性能.
  • 通过PCSK9基因淘汰,有效的siRNA干扰得到了证实.

结论:

  • 交联离子移植的德克斯涂层显著提高了聚合物/核酸复合物的血液稳定性和传染效率.
  • 这种新的三元传递系统展示了作为核酸治疗的成本效益高,下一代平台的潜力.
  • 这种方法为设计先进的传递载体提供了宝贵的见解,为具有挑战性的基因疗法应用提供了性能增强的先进传递载体.