School of Energy and Environmental Engineering, University of Science and Technology Beijing, Beijing, 100083, People's Republic of China.
Shunde Graduate School of University of Science and Technology Beijing, Shunde, Guangdong Province, 528399, People's Republic of China.
Int J Nanomedicine. 2023 Jan 22;18:425-436. doi: 10.2147/IJN.S397721. eCollection 2023.
A good understanding of the adhesion behaviors of the nanocarriers in microvessels in chemo-hyperthermia synergistic therapy is conducive to nanocarrier design for targeted drug delivery.
In this study, we constructed an artificial blood vessel system using gelatins with a complete endothelial monolayer formed on the inner vessel wall. The numbers of adhered NPs under different conditions were measured, as well as the interaction forces between the arginine-glycine-aspartic acid (RGD) ligands and endothelial cells.
The experimental results on the adhesion of ligand-coated nanoparticles (NPs) with different sizes and morphologies in the blood vessel verified that the gelatin-based artificial vessel possessed good cytocompatibility and mechanical properties, which are suitable for the investigation on NP adhesion characteristics in microvessels. When the temperature deviated from 37 °C, an increase or decrease in temperature resulted in a decrease in the number of adhered NPs, but the margination probability of NP adhesion increased at high temperatures due to the enhanced Brownian movement and flow disturbance. It is found that the effect of cooling was less than that of heating according to the observed changes in cell morphology and a decrease in cell activity under the static and perfusion culture conditions within the temperature range of 25 °C-43 °C. Furthermore, the measurement results of change in the RGD ligand-cell interaction with temperature showed good agreement with those in the number of adhered NPs.
The Findings suggest that designing ligands that can bind to the receptor and are least susceptible to temperature variation can be an effective means to enhance drug retention.
深入了解纳米载体在化疗-热疗协同治疗中在微血管中的黏附行为，有利于设计用于靶向药物输送的纳米载体。
本研究构建了一种使用完整内皮单层形成在内腔壁上的明胶的人工血管系统。测量了在不同条件下黏附的 NPs 的数量，以及精氨酸-甘氨酸-天冬氨酸 (RGD) 配体与内皮细胞之间的相互作用力。
在血管中黏附具有不同大小和形态的配体包覆的纳米颗粒 (NPs) 的实验结果验证了基于明胶的人工血管具有良好的细胞相容性和机械性能，非常适合研究 NPs 在微血管中的黏附特性。当温度偏离 37°C 时，温度升高或降低都会导致黏附的 NPs 数量减少，但由于布朗运动和流动干扰增强，高温会导致 NP 黏附的靠边概率增加。根据在 25°C-43°C 温度范围内静态和灌注培养条件下观察到的细胞形态变化和细胞活性下降，发现冷却的效果小于加热的效果。此外，与黏附的 NPs 数量的变化相关的 RGD 配体-细胞相互作用的测量结果与那些结果吻合良好。
这些发现表明，设计能够与受体结合且对温度变化最不敏感的配体可能是增强药物保留的有效手段。
