IMECH-IR  > 非线性力学国家重点实验室
Alternative TitleMolecular Dynamics Simulations of PEGylated Nanoparticles Passing through Pulmonary Surfactant Monolayer
Thesis Advisor胡国庆
Degree Grantor中国科学院大学
Place of Conferral北京
Degree Discipline流体力学






Other Abstract

Design of nanoparticles (NPs) for drug delivery to human body receives the increasing concerns. As a major means of drug delivery, lung organs have advantages over other methods including oral administration and injection. This is due to the high permeability of the lungs, the properties of substance exchange of large surface area, and the non-invasive nature of pulmonary administration. However, there are still many challenges for drugs to enter the circulatory system through the lungs, among which the main obstacle is the pulmonary surfactant (PS) membrane. The PS is composed of 85% phospholipids, 5% cholesterol and 10% protein. It can be adsorbed at the gas-liquid interface and encapsulates the fluid in the lungs as a monolayer, thereby reducing surface tension and maintaining normal breathing. When particles reach deep into the lung, they inevitably interact with the PS monolayer. Whether NPs can pass through the barrier depends on the physicochemical properties of the particle surface and the biophysical properties of the membrane surface.

NPs for drug delivery are always surface-modified to increase their bio-compatibility or functionality by regulating their surface properties. Grafting with polymers is efficient to eliminate the adsorption of proteins for NPs. Designing encapsulated NPs has been focusing on controlling and changing the properties of modified materials. A number of biochemical experiments have pointed out the importance of grafting the polymer, and the degree of NPs entering the PS monolayer depends on the type of polymer, the modification mode of polymer, surface charge of NPs and other factors

A coarse-grained molecular dynamics model and a gold nanoparticle coarse-grained model modified with polyethylene glycol (PEG) were established to describe the structure and molecular behavior of the real and natural PS monolayer. The interaction between the PEGylated nanoparticle and PS monolayer is studied by coarse-grained molecular dynamic simulations. The effect of PEG modification on the trans-membrane effect of NPs and the change of the structure and biophysical properties of the NPs on the PS monolayer were quantitatively studied. The results indicate that PEG chains with negative charge, low PEG density, and appropriate PEG chain length are more favorable for membrane penetration.

The biophysical properties of PS monolayer have important influence on the trans-membrane of NPs. The surface tension is the most important biophysical property of the PS monolayer. Using Martini coarse-grained simulations,

we explore the interaction between PS monolayer and PEGylated nanoparticle under different monolayer surface tension. It is found that the higher the surface tension of PS monolayer, the better the NPs can pass through the PS monolayer. In addition, we find that the protein components in the PS monolayer are favorable for the trans-membrane penetration of NPs, and the components of PS monolayer are consumed by the way of pulling out phospholipids and proteins during the trans-membrane penetration of NPs.

These studies have deepened the understanding of the interaction between NPs and the PS monolayer by surface modification and provided important information for guiding the design of more advantageous nano-drugs.

Call NumberMas2019-008
Document Type学位论文
Recommended Citation
GB/T 7714
李木均. PEG修饰的纳米颗粒穿过肺表面活性剂单层膜的分子动力学模拟[D]. 北京. 中国科学院大学,2019.
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