School of Chemistry and Chemical Engineering, Guangdong Provincial Key Lab for Green Chemical Product Technology, South China University of Technology , Guangzhou 510640, P. R. China.
Langmuir. 2017 Dec 19;33(50):14480-14489. doi: 10.1021/acs.langmuir.7b03544. Epub 2017 Dec 6.
Surface functionalization of nanoparticles (NPs) with stealth polymers (e.g., hydrophilic and zwitterionic polymers) has become a common strategy to resist nonspecific protein adsorption recently. Understanding the role of surface decoration on NP-biomembrane interactions is of great significance to promote the application of NPs in biomedical fields. Herein, using coarse-grained molecular dynamics (CGMD) simulations, we investigate the interactions between stealth polymer-coated gold nanoparticles (AuNPs) and lipid membranes. The results show that AuNPs grafted with zwitterionic polymers can more easily approach the membrane surface than those coated with hydrophilic poly(ethylene glycol) (PEG), which can be explained by the weak dipole-dipole interaction between them. For zwitterionic AuNPs which can undergo pH-dependent charge conversion, different interaction modes which depend on the polymer protonation degree are found. When the protonation degree is low, the particles just adsorb on the membrane surface; at moderate protonation degrees, the particles can directly translocate across the lipid membrane through a transient hydrophilic pore formed on the membrane surface; the particles are fully wrapped by the curved lipid membrane at high protonation degrees, which may lead to endocytosis. Finally, the effect of polymer chain length on the cellular uptake of zwitterionic polymer-coated AuNPs is considered. The results demonstrate that longer polymer chain length will block the translocation of AuNPs across the lipid membrane when the protonation degree is not high; however, it can improve the transmembrane efficiency of AuNPs at high protonation degrees. We expect that these findings are of immediate interest to the design and synthesis of pH-responsive nanomaterials based on zwitterionic polymers and can prompt their further applications in the field of biomedicine.
纳米粒子（NPs）的表面功能化最近采用了隐身聚合物（例如亲水性和两性离子聚合物），成为抵抗非特异性蛋白质吸附的常见策略。了解表面修饰对 NP-生物膜相互作用的作用对于促进 NPs 在生物医学领域的应用具有重要意义。在此，我们使用粗粒化分子动力学（CGMD）模拟研究了隐身聚合物涂覆的金纳米粒子（AuNPs）与脂质膜之间的相互作用。结果表明，与涂覆有亲水性聚乙二醇（PEG）的 AuNPs 相比，带有两性离子聚合物的 AuNPs 更容易接近膜表面，这可以通过它们之间的弱偶极-偶极相互作用来解释。对于可以进行 pH 依赖性电荷转换的两性离子 AuNPs，发现了依赖于聚合物质子化程度的不同相互作用模式。当质子化程度较低时，颗粒仅吸附在膜表面上；在中等质子化程度下，颗粒可以直接通过在膜表面上形成的瞬时亲水孔穿过脂质膜进行直接易位；在高质子化程度下，颗粒完全被弯曲的脂质膜包裹，这可能导致内吞作用。最后，考虑了聚合物链长对两性离子聚合物涂覆的 AuNPs 细胞摄取的影响。结果表明，当质子化程度不高时，较长的聚合物链长会阻止 AuNPs 穿过脂质膜的易位；然而，它可以提高高质子化程度下 AuNPs 的跨膜效率。我们期望这些发现对基于两性离子聚合物的 pH 响应纳米材料的设计和合成具有直接的兴趣，并可以促使它们在生物医学领域的进一步应用。
