| Autor: |
Zhao HY; College of Engineering and Applied Sciences, MOE Key Laboratory of High Performance Polymer Materials & Technology, Nanjing University, Nanjing, 210033, China., Chen YQ; Center for Soft Condensed Matter Physics and Interdisciplinary Research, School of Physical Science and Technology, Soochow University, Suzhou, 215031, China., Luo XY; College of Engineering and Applied Sciences, MOE Key Laboratory of High Performance Polymer Materials & Technology, Nanjing University, Nanjing, 210033, China., Cai MJ; College of Engineering and Applied Sciences, MOE Key Laboratory of High Performance Polymer Materials & Technology, Nanjing University, Nanjing, 210033, China., Li JY; School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China., Lin XY; School of Stomatology, Nanjing Medical University, Nanjing, 211166, China., Zhang H; Department of Oncology, the First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, China., Ding HM; Center for Soft Condensed Matter Physics and Interdisciplinary Research, School of Physical Science and Technology, Soochow University, Suzhou, 215031, China., Jiang GL; Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China., Hu Y; College of Engineering and Applied Sciences, MOE Key Laboratory of High Performance Polymer Materials & Technology, Nanjing University, Nanjing, 210033, China. |
| Abstrakt: |
Neutral nanomaterials functionalized with PEG or similar molecules have been popularly employed as nanomedicines. Compared to positive counterparts that are capable of harnessing the well-known proton sponge effect to facilitate their escape from lysosomes, it is yet unclear how neutral substances got their entry into the cytosol. In this study, by taking PEGylated, neutral Au nanospheres as an example, we systematically investigated their time-dependent translocation postuptake. Specifically, we harnessed dissipative particle dynamics simulations to uncover how nanospheres bypass lysosomal entrapment, wherein a mechanism termed as "squeezing-out" mode was discovered. We next conducted a comprehensive investigation on how nanomaterials implicate lysosomes in terms of integrity and functionality. By using single-molecule imaging, specific preservation of PEG-terminated with targeting moieties in lysosomes supports the "squeezing-out" mode as the mechanism underlying the lysosomal escape of nanomaterials. All evidence points out that such a process is benign to lysosomes, wherein the escape of nanomaterials proceeds at the expense of targeting moieties loss. Furthermore, we proved that by fine-tuning of the efficacy of nanomaterials escaping from lysosomes, modulation of distinct pathways and metabolic machinery can be achieved readily, thereby offering us a simple and robust tool to implicate cells. |
