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

文献类型：期刊论文

作者Jiang, Xiaohe5,6; Xu, Sai4,5; Miao, Yunqiu6; Huang, Kang4,5; Wang, Bingqi5,6; Ding, Bingwen5,6; Zhang, Zhuan3,6; Zhao, Zitong6; Zhang, Xinxin2,6; Shi, Xinghua4,5
刊名PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
出版日期2024-05-28
卷号121期号:22页码:11
关键词interstitial fluid pressure extravasation penetration curvature nanoparticles
ISSN号0027-8424
DOI10.1073/pnas.2319880121
通讯作者Yu, Miaorong(mryu@simm.ac.cn) ; Tian, Falin(tianfl@nanoctr.cn) ; Gan, Yong(ygan@simm.ac.cn)
英文摘要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.
WOS关键词TUMOR-GROWTH ; MECHANISMS ; VISCOSITY ; STRATEGIES ; TRANSPORT ; SIZE
资助项目National Science Fund of Distinguished Young Scholars[82025032] ; National Natural Science Foundation of China[12272101] ; National Natural Science Foundation of China[82073773] ; National Key R&D Program of China[2022YFA1203200] ; Open Competition to Select the Best Candidates Key Technology Program for Nucleic Acid Drugs of NCTIB[NCTIB2022HS01006] ; Key Research Program of Chinese Academy of Sciences[ZDBS-ZRKJZ-TLC005] ; Young Elite Scientists Sponsorship Program by CAST[2022QNRC001]
WOS研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:001237489500003
出版者NATL ACAD SCIENCES
源URL[http://119.78.100.183/handle/2S10ELR8/311761]  
专题新药研究国家重点实验室
通讯作者Yu, Miaorong; Tian, Falin; Gan, Yong
作者单位1.Natl Inst Food & Drug Control, Natl Med Prod Adm, Key Lab Qual Res & Evaluat Pharmaceut Excipients, Beijing 100050, Peoples R China
2.Henan Univ, Sch Pharm, Kaifeng 475004, Peoples R China
3.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China
4.Chinese Acad Sci, Ctr Excellence Nanosci, Natl Ctr Nanosci & Technol, Beijing 100190, Peoples R China
5.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
6.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Jiang, Xiaohe,Xu, Sai,Miao, Yunqiu,et al. Curvature- mediated rapid extravasation and penetration of nanoparticles against interstitial fluid pressure for improved drug delivery[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2024,121(22):11.
APA Jiang, Xiaohe.,Xu, Sai.,Miao, Yunqiu.,Huang, Kang.,Wang, Bingqi.,...&Gan, Yong.(2024).Curvature- mediated rapid extravasation and penetration of nanoparticles against interstitial fluid pressure for improved drug delivery.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,121(22),11.
MLA Jiang, Xiaohe,et al."Curvature- mediated rapid extravasation and penetration of nanoparticles against interstitial fluid pressure for improved drug delivery".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 121.22(2024):11.

入库方式： OAI收割

来源：上海药物研究所

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