Zhanlin Zhang,Hui Yan,Shang Li,Yuan Liu,Pan Ran,Weijia Chen,Xiaohong Li
The navigation of drug-loaded nanocarriers is confronted with series of physiological and pathological barriers in blood circulation, tissue penetration and cell internalization. In the current study, self-propelled micromotors of fiber rods are proposed to address the transportation barriers of chemotherapeutic drugs. Fiber rods with distinct Janus structure are prepared by side-by-side electrospinning, and urease and folate are conjugated on the respective sides of Janus rods (JRs) as power source and targeting ligands of Janus micromotors (JMs). The grafting density of urease determines the motion velocity and trajectory of JMs, and the high motion velocity and large mean-square displacement are detected in both phosphate-buffered saline and simulated extracellular matrices of tumor tissues. Despite no interference with the uptake pathway, the self-propelled motion promotes the folate-mediated cell internalization of JMs and maximizes the toxicities and apoptosis rate of tumor cells. The self-propulsion force from one side of JMs enhances the lateral drift and extravasation across blood vessel walls, increasing their accumulation in tumor tissues by around 2 folds and, doxorubicin accumulation, by around 2.6 folds. The treatment with JMs remarkably inhibits the tumor growth, prolongs the animal survival rate and induces strong tumor necrosis without obvious histopathological and hematological abnormalities to normal tissues. Thus, this study demonstrates a feasible strategy in combating the navigation barriers of blood vessel extravasation, tumor tissue diffusion and cell capture, effectively promoting the treatment efficacy and alleviating side effects of chemotherapeutic agents.
Jiabin Zhang,Yanteng Xu,Chenya Zhuo,Run Shi,Haixia Wang,Zuquan Hu,Hon Fai Chan,Hae-Won Kim,Yu Tao,Mingqiang Li
Engineering hepatocytes as multicellular cell spheroids can improve their viability after implantation in vivo for effective rescue of the devastating acute liver failure (ALF). However, there is still a lack of straightforward methods for efficient generation of functional hepatocyte spheroids. In this study, a magnetic system, consisting of magnetic microwell arrays and magnet blocks, is developed to realize magnetically controlled 3D cell capture and spatial confinement-mediated cell aggregation. The cell spheroids with smaller size show superior hepatic functions than the larger-sized counterparts. Notably, the intrinsic magnetism of magnetic microwell arrays can regulate superoxide anions in hepatocyte spheroids and herein promote various biological processes , including antioxidation, hepatocyte-related functions, and pro-angiogenic potential. Ectopic implantation of the functional cell spheroids in ALF-challenged mice significantly prolongs the animal survival, ameliorates inflammation, and promotes liver regeneration . Hence, application of the magnetic system for generation of functionally enhanced hepatocyte spheroids holds great potential for clinical translation in the future.
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