Li Mengqi, Gao Zhiliang, Lv Huiyuan, Sekhar Kanaparedu P C, Song Aixin, Jiang Xinyi, Hao Jingcheng, Cui Jiwei
Key Laboratory of Colloid and Interface Chemistry of the Ministry of Education, School of Chemistry and Chemical Engineering, Shandong University, Jinan, Shandong 250100, China.
Shandong Key Laboratory of Targeted Drug Delivery and Advanced Pharmaceutics, Shandong University, Jinan, Shandong 250100, China.
ACS Nano. 2025 Jun 24;19(24):22240-22252. doi: 10.1021/acsnano.5c03978. Epub 2025 Jun 9.
Stiffness, as a crucial physicochemical property of nanoparticles (NPs), has demonstrated a significant impact on bio-nano interactions, including blood circulation, biodistribution, tumor accumulation, and cellular uptake. However, the potential role of NP stiffness in modulating bio-nano interactions to potentiate drug delivery efficacy remains largely unexplored. In this study, poly(ethylene glycol) (PEG) NPs are engineered by the sophisticated layer-by-layer (LbL) assembly approach, and the Young's moduli of NPs in the range of 2-31 kPa are tuned by control over the bilayer numbers. Notably, softer PEG NPs resulted in less adsorption of the protein corona and cell association. The half-life of blood circulation time of PEG NPs decreases along with the increase in stiffness/bilayer number of NPs, while the accumulation of PEG NPs in the liver is contrary to the case. In addition, stiffness influences the targeted drug delivery efficacy, where softer PEG NPs modified with hyaluronic acid exhibited higher cell targeting and tumor accumulation as well as better inhibition of tumor growth. This work highlights the bilayer number-mediated stiffness of NPs and the vital role of stiffness in bio-nano interactions, which provides a promising approach to design nanocarriers for improved drug delivery efficacy.
硬度作为纳米颗粒（NPs）的一项关键物理化学性质，已证明对生物-纳米相互作用有重大影响，包括血液循环、生物分布、肿瘤蓄积和细胞摄取。然而，NP硬度在调节生物-纳米相互作用以增强药物递送功效方面的潜在作用仍 largely未被探索。在本研究中，聚乙二醇（PEG）纳米颗粒通过复杂的层层（LbL）组装方法构建，并且通过控制双层数量将NP的杨氏模量调节在2-31 kPa范围内。值得注意的是，较软的PEG纳米颗粒导致蛋白质冠层的吸附和细胞结合较少。PEG纳米颗粒血液循环时间的半衰期随着NP硬度/双层数量的增加而降低，而PEG纳米颗粒在肝脏中的蓄积情况则相反。此外，硬度影响靶向药物递送功效，其中用透明质酸修饰的较软PEG纳米颗粒表现出更高的细胞靶向性和肿瘤蓄积以及对肿瘤生长的更好抑制作用。这项工作突出了NP的双层数量介导的硬度以及硬度在生物-纳米相互作用中的重要作用，这为设计用于提高药物递送功效的纳米载体提供了一种有前景的方法。
