Chinese scholars have made new progress in the research of tumor mechanical microenvironment and nanoparticle transport mechanism

Figure Tumor mechanical microenvironment and proliferation of nanoparticles

With the support of the National Natural Science Foundation of China (grant numbers: 12225208, 11972280, 12202193), the team of Professor Xu Feng from the Institute of Biomimetic Engineering and Biomechanics (BEBC) of Xi'an Jiaotong University systematically studied the influence mechanism of mechanical factors in the tumor microenvironment on the diffusion of nanoparticles, and made new progress
in the research of tumor mechanical microenvironment and nanoparticle transport mechanism 。 The research results, titled "Extracellular Matrix Physical Properties Govern the Diffusion of Nanoparticles in Tumor Microenvironment," were published in the Proceedings of the National Academy of Sciences on December 27, 2022 published online in the National Academy of Sciences of the United States of America (PNAS
).
Link to the paper: _istranslated="1">.

Nanotechnology is widely used in biomedicine, information industry, environmental industry, energy and environmental protection and other fields, among which nanoparticles with nanomaterials as the carrier have great application prospects in the field of cancer diagnosis and treatment, but the transmission efficiency of nanoparticles in vivo is low, which has become a key bottleneck
restricting the development of nanomedicine.
In view of the difficulty of transmission of nanoparticles in vivo, current research mainly focuses on the design and regulation of the morphology, biochemistry and mechanical properties of the nanoparticles themselves
.
In the process of tumor development and development, the extracellular matrix (ECM) of the tumor will also undergo a series of changes in physical and especially mechanical properties, which seriously hinder the spread
of nanoparticles.
As an important physical barrier for the transport of nanoparticles in the body, the mechanical properties of ECM affect the diffusion of nanoparticles is unclear
.
Therefore, it is crucial
to study the diffusion behavior of nanoparticles in tumor ECM and elucidate the influence mechanism of ECM on the spread of nanoparticles.

The research team characterized the changes of the mechanical properties of clinical tumor tissues through statistical analysis of clinical samples, and found that the fiber density and stiffness of the ECM were significantly increased, the fiber structure was arranged in a one-way straight line, and the diffusion ability of nanoparticles in the tumor tissue ECM was significantly reduced.
Based on molecular dynamics simulation, combined with the analysis of particle motion trajectories and interaction parameters with the network, the influence of tumor ECM density, stiffness and fiber arrangement on the diffusion of nanoparticles was clarified, and the mechanical mechanism
of ECM stiffness affecting the diffusion behavior of particles by regulating the dynamic fluctuation of nanoparticles in contact with the network was revealed 。 This work not only innovatively reveals the key micromechanical mechanism of the interaction between the tumor mechanical microenvironment and nanoparticles, and the important influence mechanism of the mechanical properties of the tumor microenvironment on the diffusion ability of nanoparticles, but also proposes a method model for comprehensively predicting and evaluating the delivery efficiency of nanoparticles based on the characterization results of the mechanical properties of the tumor microenvironment, which provides a theoretical basis and method guidance
for studying the mass transfer and mechanical mechanism in the tumor mechanical microenvironment.