Curvature- mediated rapid extravasation and penetration of nanoparticles against interstitial fluid pressure for improved drug delivery

• 成果类型: Article
• 署名作者: Jiang, Xiaohe; Xu, Sai; Miao, Yunqiu; Huang, Kang; Wang, Bingqi; Ding, Bingwen; Zhang, Zhuan; Zhao, Zitong; Zhang, Xinxin; Shi, Xinghua; Yu, Miaorong; Tian, Falin; Gan, Yong
• 署名单位: Chinese Academy of Sciences; Shanghai Institute of Materia Medica, CAS; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; Chinese Academy of Sciences; National Center for Nanoscience & Technology, CAS; Nanjing University of Chinese Medicine; Henan University; National Institute of Food & Drug Control - China
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-12107
• DOI: 10.1073/pnas.2319880121
• 发表日期: 2024-05-28
• 关键词: tumor-growth; mechanisms; viscosity; strategies; transport; size

摘要

Elevated interstitial fluid pressure (IFP) within pathological tissues (e.g., tumors, obstructed kidneys, and cirrhotic livers) creates a significant hindrance to the transport of nanomedicine, ultimately impairing the therapeutic efficiency. Among these tissues, solid tumors present the most challenging scenario. While several strategies through reducing tumor IFP have been devised to enhance nanoparticle delivery, few approaches focus on modulating the intrinsic properties of nanoparticles to effectively counteract IFP during extravasation and penetration, which are precisely the stages obstructed by elevated IFP. Herein, we propose an innovative solution by engineering nanoparticles with a fusiform shape of high curvature, enabling efficient surmounting of IFP barriers during extravasation and penetration within tumor tissues. Through experimental and theoretical analyses, we demonstrate that the elongated nanoparticles with the highest mean curvature outperform spherical and rod - shaped counterparts against elevated IFP, leading to superior intratumoral accumulation and antitumor efficacy. Superresolution microscopy and molecular dynamics simulations uncover the underlying mechanisms in which the high curvature contributes to diminished drag force in surmounting high - pressure differentials during extravasation. Simultaneously, the facilitated rotational movement augments the hopping frequency during penetration. This study effectively addresses the limitations posed by high - pressure impediments, uncovers the mutual interactions between the physical properties of NPs and their environment, and presents a promising avenue for advancing cancer treatment through nanomedicine.