Chen Haoran, Liu Yu-Cheng, Zhang Zhiming, Li Moxin, Du Lidong, Wu Pei-Chun, Chong Wai-How, Ren Fuzeng, Zheng Weiming, Liu Tzu-Ming
Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, China.
Department of Materials Science and Engineering, Southern University of Science and Technology, Shenzhen, China.
Front Chem. 2022 Jul 18;10:944556. doi: 10.3389/fchem.2022.944556. eCollection 2022.
Remarkable advancement has been made in the application of nanoparticles (NPs) for cancer therapy. Although NPs have been favorably delivered into tumors by taking advantage of the enhanced permeation and retention (EPR) effect, several physiological barriers present within tumors tend to restrict the diffusion of NPs. To overcome this, one of the strategies is to design NPs that can reach lower size limits to improve tumor penetration without being rapidly cleared out by the body. Several attempts have been made to achieve this, such as selecting appropriate nanocarriers and modifying surface properties. While many studies focus on the optimal design of NPs, the influence of mouse strains on the effectiveness of NPs remains unknown. Therefore, this study aimed to assess whether the vascular permeability of NPs near the lower size limit differs among mouse strains. We found that the vessel permeability of dextran NPs was size-dependent and dextran NPs with a size below 15 nm exhibited leakage from postcapillary venules in all strains. Most importantly, the leakage rate of 8-nm fluorescein isothiocyanate dextran was significantly higher in the BALB/c mouse strain than in other strains. This strain dependence was not observed in slightly positive TRITC-dextran with comparable sizes. Our results indicate that the influence on mouse strains needs to be taken into account for the evaluation of NPs near the lower size limit.
纳米颗粒（NPs）在癌症治疗中的应用取得了显著进展。尽管纳米颗粒利用增强渗透与滞留（EPR）效应已被顺利递送至肿瘤中，但肿瘤内存在的几种生理屏障往往会限制纳米颗粒的扩散。为克服这一问题，其中一种策略是设计尺寸能达到更低限度的纳米颗粒，以提高肿瘤穿透性，同时避免被机体快速清除。人们已进行了多次尝试来实现这一目标，比如选择合适的纳米载体并修饰表面性质。虽然许多研究聚焦于纳米颗粒的优化设计，但小鼠品系对纳米颗粒有效性的影响仍不清楚。因此，本研究旨在评估尺寸接近下限的纳米颗粒在不同小鼠品系中的血管通透性是否存在差异。我们发现葡聚糖纳米颗粒的血管通透性具有尺寸依赖性，且尺寸小于15 nm的葡聚糖纳米颗粒在所有品系中均表现出从毛细血管后微静脉渗漏。最重要的是，8 nm异硫氰酸荧光素葡聚糖在BALB/c小鼠品系中的渗漏率显著高于其他品系。在尺寸相当的略带阳性的四甲基罗丹明异硫氰酸酯葡聚糖中未观察到这种品系依赖性。我们的结果表明，在评估尺寸接近下限的纳米颗粒时，需要考虑对小鼠品系的影响。
