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김경환Kyunghwan Kim

울산과학기술원

Nano Today, Available online 29 March 2024 | https://doi.org/10.1016/j.nantod.2024.102242 Spatiotemporal tracking of intracellular nanoparticles using complementary imaging systems reveals acute ferroptosis triggered by burst reduction of ferric ions

Chan-Gi Pack ^a,b,1, Min Kyo Jung^c,1, Kyunghwan Kim ^d,1, Woojung Yoo^e, Minjong Kim^f, Minju Cho ^a,g, Myoung-Hee Kang ^e, Sanghwa Lee ^a,g, Jisu Im ^e, In Ki Kim ^a,b, Sang-Wook Lee ^b,h, Jun Ki Kim ^a,g, Jinmyoung Joo ^e,i,j,k

^aDepartment of Biomedical Engineering, Brain Korea 21 Project, University of Ulsan College of Medicine, Seoul 05505, South Korea

^bConvergence Medicine Research Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul 05505, South Korea

^cDepartment of Structure and Function of Neural Network, Korea Brain Research Institute, Daegu 41068, South Korea

^dDepartment of Chemistry, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, South Korea

^eDepartment of Biomedical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, South Korea

^fDepartment of Biological Science, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, South Korea

^gBiomedical Engineering Research Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul 05505, South Korea

^hDepartment of Radiation Oncology, University of Ulsan College of Medicine, Seoul 05505, South Korea

ⁱCenter for Genomic Integrity, Institute for Basic Science, Ulsan 44919, South Korea

^jGraduate School of Health Science and Technology, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, South Korea

^kMaterials Research Science and Engineering Center, University of California, San Diego, La Jolla, CA 92093, United States

¹These authors contribute equally to this work.

Corresponding authors: Jun Ki Kim, Jinmyoung Joo

Abstract

Uptake and intracellular trafficking of nanoparticles are tightly regulated by their interactions with cellular organelles and physiological microenvironment. Although the dynamic physicochemical reactions at the interface of nanoparticles and cells ultimately determine the intracellular distribution and fate, microscopic tracing and quantitative analysis of the nanoparticles have been hampered by the limited resolution associated with individual nanoparticle trafficking. Herein, we report spatiotemporal investigations on autophagic clearance of biodegradable iron oxide-silica core-shell nanoparticles in terms of intracellular trafficking and ionic dissolution at a single cell level using multimodal imaging systems. By combining transmission electron microscopy and super-resolution confocal laser scanning microscopy with fluorescence correlation spectroscopy, the complementary imaging analysis exclusively shows the intracellular uptake, endosomal fusion and biodegradative clearance, leading to identify the step-by-step endocytic transport pathway and autophagic degradation pathways. Tracing the intracellular trafficking of nanoparticles reveals that they are spontaneously transported from endosomes to lysosomes, and transiently stimulate autophagy while maintaining cell viability. While protecting iron oxide core, the silica shell is gradually degraded during endocytosis and autophagic clearance, resulting in ionic dissolution of iron oxide in acidic environment. Moreover, burst reduction of ferric ions by adding ascorbic acid readily triggers acute ferroptosis owing to rapid supplement of ferrous ions and Fenton reaction in cancer cells. The complementary imaging strategy provides insights into the design of biocompatible nanomedicines for cellular delivery and the degradative mechanisms beyond the intracellular fate.

논문정보

형식Research article
게재일2024년 03월 (BRIC 등록일 2024-04-01)
연구진국내(교신)+국외 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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