title: Mitophagy induced by nanoparticle-peptide conjugates enabling an alternative intracellular trafficking route.
abstract: The intracellular behaviors of nanoparticles are fundamentally important for the evaluation of their biosafety and the designs of nano carrier-assisted drug delivery with high therapeutic efficacy. It is still in a great need to discover how functionalized nanoparticles are transported inside the cells, for instance, in a complicated fashion of translocation between different types of cell organelles. Here we report a new understanding of the interactions between nanoparticles and cells by the development of polyoxometalates nanoparticle-peptide conjugates and investigation of their intracellular trafficking behaviors. The as-prepared nanoparticles are featured with a unique combination of fluorescence and high contrast for synchrotron X-ray-based imaging. Functional surface modification with peptides facilitates effective delivery of the nanoparticles onto the target organelle (mitochondria) and subsequent intracellular trafficking in a dynamic mode. Interestingly, our experimental results have revealed that autophagy of mitochondria (mitophagy) can be induced by NP-peptide as a cellular response for recycling the damaged organelles, through molecular mediation associated with the change of mitochondrial membrane potential. The biological effects induced by NP-peptide reciprocally affect the distribution patterns and fates of nanoparticles in the cell metabolism by providing an alternative route of intracellular trafficking. The new understanding of the mutual activities between nanoparticles and cells will enrich our approaches in the development of nanobiotechnology and nano-medicine for disease treatments.
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, 199 RenAi Road, Suzhou Industrial Park, Suzhou City, Jiangsu Province 215123, China.
authors.forename: Zhaolei
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, 199 RenAi Road, Suzhou Industrial Park, Suzhou City, Jiangsu Province 215123, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.affiliation: College of Pharmaceutical Sciences, Soochow University, 199 RenAi Road, Suzhou Industrial Park, Suzhou City, Jiangsu Province 215123, China.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, 199 RenAi Road, Suzhou Industrial Park, Suzhou City, Jiangsu Province 215123, China.
authors.forename: Jinyin
authors.initials: J
authors.lastname: Liu
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, 199 RenAi Road, Suzhou Industrial Park, Suzhou City, Jiangsu Province 215123, China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Xing
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, 199 RenAi Road, Suzhou Industrial Park, Suzhou City, Jiangsu Province 215123, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhong
authors.affiliation: College of Pharmaceutical Sciences, Soochow University, 199 RenAi Road, Suzhou Industrial Park, Suzhou City, Jiangsu Province 215123, China.
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Xu
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, 199 RenAi Road, Suzhou Industrial Park, Suzhou City, Jiangsu Province 215123, China.
authors.forename: Zhenhui
authors.initials: Z
authors.lastname: Kang
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, 199 RenAi Road, Suzhou Industrial Park, Suzhou City, Jiangsu Province 215123, China. Electronic address: jliu@suda.edu.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
mesh_terms: D006801:Humans; D061986:MCF-7 Cells; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D063306:Mitophagy / Q000187:drug effects*; D008958:Models, Molecular; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010455:Peptides / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D017973:Tungsten Compounds / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D000099294:Polyoxometalates
chemical_list: D010455:Peptides; D017973:Tungsten Compounds; C102296:polyoxometalate I; D000099294:Polyoxometalates
keywords: Intracellular trafficking; Mitochondria-targeting; Mitophagy; Nanoparticles; Peptides