title: Mitochondria-Targeting Magnetic Composite Nanoparticles for Enhanced Phototherapy of Cancer.
abstract: Photothermal therapy (PTT) and photodynamic therapy (PDT) are promising cancer treatment modalities in current days while the high laser power density demand and low tumor accumulation are key obstacles that have greatly restricted their development. Here, magnetic composite nanoparticles for dual-modal PTT and PDT which have realized enhanced cancer therapeutic effect by mitochondria-targeting are reported. Integrating PTT agent and photosensitizer together, the composite nanoparticles are able to generate heat and reactive oxygen species (ROS) simultaneously upon near infrared (NIR) laser irradiation. After surface modification of targeting ligands, the composite nanoparticles can be selectively delivered to the mitochondria, which amplify the cancer cell apoptosis induced by hyperthermia and the cytotoxic ROS. In this way, better photo therapeutic effects and much higher cytotoxicity are achieved by utilizing the composite nanoparticles than that treated with the same nanoparticles missing mitochondrial targeting unit at a low laser power density. Guided by NIR fluorescence imaging and magnetic resonance imaging, then these results are confirmed in a humanized orthotropic lung cancer model. The composite nanoparticles demonstrate high tumor accumulation and excellent tumor regression with minimal side effect upon NIR laser exposure. Therefore, the mitochondria-targeting composite nanoparticles are expected to be an effective phototherapeutic platform in oncotherapy.
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science and Laboratory of Advanced Materials, Fudan University, Shanghai, 200433, P. R. China.
authors.forename: Ranran
authors.initials: R
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science and Laboratory of Advanced Materials, Fudan University, Shanghai, 200433, P. R. China.
authors.forename: Haibao
authors.initials: H
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science and Laboratory of Advanced Materials, Fudan University, Shanghai, 200433, P. R. China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
authors.affiliation: School of Pharmacy & Key Laboratory of Smart Drug Delivery, Fudan University, Shanghai, 201203, P. R. China.
authors.forename: Shun
authors.initials: S
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science and Laboratory of Advanced Materials, Fudan University, Shanghai, 200433, P. R. China.
authors.forename: Wuli
authors.initials: W
authors.lastname: Yang
mesh_terms: D000072283:A549 Cells; D000818:Animals; D003952:Diagnostic Imaging; D004705:Endocytosis; D005453:Fluorescence; D006801:Humans; D007208:Indocyanine Green / Q000378:metabolism; D060328:Magnetic Phenomena; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000473:pathology / Q000628:therapy*; D010789:Phototherapy; D017382:Reactive Oxygen Species / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D017382:Reactive Oxygen Species; D007208:Indocyanine Green
keywords: magnetic composite nanoparticles; mitochondria-targeting; multimode imaging; photodynamic therapy; photothermal therapy