title: Multimodal Upconversion Nanoplatform with a Mitochondria-Targeted Property for Improved Photodynamic Therapy of Cancer Cells.
abstract: Upconversion nanoparticles (UCNPs) with the capacity to emit high-energy visible or UV light under low-energy near-infrared excitation have been extensively explored for biomedical applications including imaging and photodynamic therapy (PDT) against cancer. Enhanced cellular uptake and controlled subcellular localization of a UCNP-based PDT system are desired to broaden the biomedical applications of the system and to increase its PDT effect. Herein, we build a multimodal nanoplatform with enhanced therapeutic efficiency based on 808 nm excited NaYbF4:Nd@NaGdF4:Yb/Er@NaGdF4 core-shell-shell nanoparticles that have a minimized overheating effect. The photosensitizer pyropheophorbide a (Ppa) is loaded onto the nanoparticles capped with biocompatible polymers, and the nanoplatform is functionalized with transcriptional activator peptides as targeting moieties. Significantly increased cellular uptake of the nanoparticles and dramatically elevated photocytotoxicity are achieved. Remarkably, colocalization of Ppa with mitochondria, a crucial subcellular organelle as a target of PDT, is proven and quantified. The subsequent damage to mitochondria caused by this colocalization is also confirmed to be significant. Our work provides a comprehensively improved UCNP-based nanoplatform that maintains great biocompatibility but shows higher photocytotoxicity under irradiation and superior imaging capabilities, which increases the biomedical values of UCNPs as both nanoprobes and carriers of photosensitizers toward mitochondria for PDT.
authors.affiliation: City University of Hong Kong Shenzhen Research Institute , Shenzhen 518057, P. R. China.
authors.forename: Xiaoman
authors.initials: X
authors.lastname: Zhang
authors.affiliation: City University of Hong Kong Shenzhen Research Institute , Shenzhen 518057, P. R. China.
authors.forename: Fujin
authors.initials: F
authors.lastname: Ai
authors.forename: Tianying
authors.initials: T
authors.lastname: Sun
authors.affiliation: City University of Hong Kong Shenzhen Research Institute , Shenzhen 518057, P. R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: City University of Hong Kong Shenzhen Research Institute , Shenzhen 518057, P. R. China.
authors.forename: Guangyu
authors.initials: G
authors.lastname: Zhu
mesh_terms: D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010316:Particle Size; D010778:Photochemotherapy; D017382:Reactive Oxygen Species / Q000378:metabolism; D013499:Surface Properties
chemical_list: D001672:Biocompatible Materials; D017382:Reactive Oxygen Species