在血管内应用时,即,癌症治疗,纳米粒子(NPs)需要通过血液循环,维持血清蛋白相互作用,在它们穿透血管并到达目标位置以释放有效载荷药物之前。对于这样的交付过程,很难理解NP表面的形态变化并评估其对靶向递送的相关影响。在这里,我们使用具有不同表面修饰的二氧化硅NP来证明NP-血液蛋白相互作用的应用过程中NP的形态影响,血管内皮细胞渗透,随后的靶向递送和光动力疗法疗效以及形态学设计用于追求高载药量.与固体和介孔NP相比,我们发现尖刺管状NPs有助于保留NPs的防污特性(或“蛋白质电晕”的脱落),在体外和体内促进更好的内皮渗透和更少的破坏。这可能归因于尖状管状NP上的多个尖峰限制了NP-蛋白质相互作用区域并促进了NP-蛋白质空间位阻。在分子模拟中,我们确定NPs上的尖管状形态修饰增强了相互作用自由能,同时降低了氨基酸数量和随后与内皮细胞VE-钙粘蛋白接触的频率。因此,这些NP在减轻对VE-cadherin稳定性和内皮细胞完整性的损害方面具有优势。我们在这里的发现表明,我们可以利用表面形态修饰来设计尖刺的管状NP,为了提高NP递送效率,同时抑制血管内皮微环境的渗漏,在纳米医学在癌症治疗中的应用中与肿瘤迁移特别相关。
Upon intravascular applications, i.e., cancer treatment, nanoparticles (NPs) are required to deliver through blood circulation, sustain serum protein interactions, before they penetrate the blood vessels and reach targeted sites for payload drug release. For a delivery process as such, it is elusive and difficult to comprehend the morphological change of NP surface and evaluate associated effects on its targeted delivery. Herein, we used silica NPs with different surface modifications to demonstrate the morphological impact of NPs during the application of the NP-blood protein interaction, vascular endothelial cell penetration, subsequent targeted delivery and photodynamic therapy efficacy, and pursue high drug-load NPs with surface designs. Compared to solid and mesoporous NPs, we found the spiky tubular NPs reserved the NPs\' antifouling properties (or shedding of \"protein corona\"), promoted better endothelial penetration and less destruction in vitro and in vivo. Such effects could be attributed to their spiky surface structures, which can limit the NP-protein interaction area and promote the NP-protein steric hindrance. Further in molecular simulations, we determined that the spiky tubular morphological modification on NPs enhanced the interaction free energy and lowered the amino acids number and the subsequent frequency in contacting with VE-cadherin of vascular endothelia. As a result, the spiky tubular NPs demonstrated its advantages in mitigating damages to VE-cadherin stability and endothelial cell integrity. Exploiting such spiky tubular surface modification, we can improve the NP delivery efficiency and prohibit the leakiness of vascular endothelia, helping address challenges faced by tumor migration in nanomedicine applications for cancer therapy.