机构：[1]Med-X center for Materials, College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, China.[2]Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China.[3]Key Laboratory of Drug Targeting and Drug Delivery Systems of Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610065, China.
In recent years, live-cell-based drug delivery systems have gained considerable attention. However, shear stress, which accompanies blood flow, may cause cell death and weaken the delivery performance. In this study, we found that reducing cholesterol in macrophage plasma membranes enhanced their tumor targeting ability by more than 2-fold. Our study demonstrates that the reduced cholesterol level deactivated the mammalian target of rapamycin (mTOR) and consequently promoted the nuclear translocation of transcription factor EB (TFEB), which in turn enhanced the expression of superoxide dismutase (SOD) to reduce reactive oxygen species (ROS) induced by shear stress. A proof-of-concept system using low cholesterol macrophages attached to MXene (e.g., l-RX) was fabricated. In a melanoma mouse model, l-RX and laser irradiation treatments eliminated tumors with no recurrences observed in mice. Therefore, cholesterol reduction is a simple and effective way to enhance the targeting performance of macrophage-based drug delivery systems.
基金：
We acknowledge the support from the National Science Fund
for Excellent Young Scholars (No. 82022070), the Regional
Innovation and Development Joint Fund (No. U20A20411),
National Natural Science Foundation of China (NO.
82304402), Joint Fund for Regional Innovation Development
of the National Natural Science Foundation of China (No.
U23A20495), and the Innovation Program of Med-X Center
for Materials from Sichuan University (MCM202103).
材料科学