On May 21, Gan Yong, a researcher of the Chinese Academy of Sciences Shanghai Institute of Materia Medica, cooperated with Shi Xinghua, a researcher of the National Center for Nanoscience, and published a research paper entitled Curvature mediated Rapid Extravasation and Penetration of Nanoparticles against Interim Fluid Pressure for Improved Drug Delivery online in the Journal of the National Academy of Sciences (PNAS). This study provides a new approach for designing efficient drug delivery carriers to overcome complex barriers in vivo.

Drug carriers can precisely regulate the temporal and spatial distribution of active molecules such as small molecules, peptides, proteins, and nucleic acids in the body, playing an important role in improving the safety and efficacy of drugs. However, carriers often face complex physiological and pathological barriers in real organisms, which limit drug delivery efficiency. Before reaching the target site, the carrier needs to overcome enzyme barriers, blood circulation barriers, tissue permeation barriers, cell barriers, and intracellular transport barriers by crossing mountains and mountains. These barriers limit the delivery process of drug carriers, resulting in less than 0.7% of drugs reaching the target tissue. To address these challenges, it is crucial to study the interaction between drug carriers and biological barriers. In recent years, research has shown that the physical properties of carriers, such as shape, stiffness, scale, and surface properties, are key factors determining their interaction with biological barriers. It is expected to improve the safety and efficacy of drugs by regulating the physical properties of carriers.

The team independently designed and synthesized various drug carriers with different shapes, and characterized them using techniques such as transmission electron microscopy. Experiments have found that compared with spherical, ellipsoidal, and rod-shaped carriers, sharp spindle shaped nanocarriers (ENP5) exhibit superior extravasation and extravasation abilities in high interstitial pressure environments both in vivo and in vitro. This study evaluated the anti-tumor efficacy of different shaped carriers loaded with chemotherapy drug doxorubicin (Dox) in a mouse model. Compared to the control group, Dox@ENP5 Enhanced tumor inhibition, with a tumor inhibition rate of over 90%, and prolonging the survival cycle of HCC liver cancer mice.

Furthermore, combining ultra-high resolution microscopy observation and molecular simulation techniques, the team explored the three-dimensional motion mode and mechanical mechanism of the carrier overcoming the high interstitial pressure barrier. Research has found that in the process of extravasation of blood vessels, the high curvature of the carrier helps to reduce fluid resistance caused by pressure gradients, accelerating the migration speed of spindle shaped carriers; During the process of tissue infiltration, high curvature promotes the rotational movement of the carrier, increases its jumping frequency in the high-pressure and dense extracellular matrix, accelerates the penetration of the carrier into the deeper layers of the tumor, and improves the efficiency of drug delivery.

The research work was supported by the National Natural Science Foundation of China and the Chinese Academy of Sciences.

Paper link



The Effect and Microscopic Mechanism of Curvature Mediated Efficient Transport of Carriers