Development Of Inorganic Agents For Magnetic Resonance Imaging Guided Photothermal-based Multimodal Synergistic Therapy

Theranosics,which is a treatment combination of diagnosis and therapy into a platform,has become the core keyword in tumor research.The ideal theranostic nanoagent for tumor is a single particle that contribute to track the agent’s location,to monitor the response to the therapy,and to increase therapeutic efficacy and safety,resulting in significant precondition requirements for fabrication of the overall theronosic system.Among all existing imaging modalities used in the clinic,magnetic resonance imaging（MRI）is an optimal medical technique because of enhanced soft tissue contrast,unlimited signal penetration depth,excellent anatomic detail,non-ionizing radiation,and high spatial resolution.Recently,photothermal therapy（PTT）is a physical medical technology,possessing advantages of high selectivity,minimal invasiveness and high efficient.PTT can be able to overcome the deficiencies in traditional cancer therapy,chemotherapy and radiotherapy,such as consistent pain,severe side effects,difficult to effect a radical cure and high recurrence rate.In our group,a series of work on the preparation of defect-structured semiconductor photothermal agent and exploration of biological applications were carried out.Due to low immunogenicity,excellent biosafety and great magnetic properties,several iron-based and cobalt-based nanomaterials have been been utilized as FDA-approved agents,but it is difficult to ablate the tumor because of their poor heat efficacy.In this dissertation,Co-based and Fe-based materials have been prepared duing to the excellent magnetism performance,better biocompatibility and high heat efficiency.In order to develop the ideal theranostic agents for MRI guided PTT-based multimodal therapy,main investigations are as follows:（1）Porous cobalt sulfide hollow nanospheres with tunable optical property for magnetic resonance imaging-guided photothermal therapyWe report on a one-pot solvothermal strategy to synthesize various porous cobalt sulfide hollow nanospheres（PCSH NSs）and elucidate the relation between PCSH NSs and their optical absorption as a guide to obtain optimal photothermal therapy（PTT）agents.After PEG modification,PEG-PCSH NSs show superexcellent photothermal conversion efficiency（⁷0.1%）.A low dose（100μL,25 ppm）could completely ablate tumors under an 808 nm laser power of 0.7 W cm^-2.Additionally,they also exhibit excellent biocompatibility,good photostability and utility for magnetic resonance imaging.Our results indicate that PCSH NSs can be considered as an outstanding PTT agent and give guidance towards the design of other photothermal theranostic agents.（2）“Transformed”Fe₃S₄ tetragonal nanosheets:a high-efficiency and body-clearable agent for magnetic resonance imaging guided photothermal and chemodynamic synergistic therapyWe have developed a transformed theranostic platform,employing PVP coated Fe₃S₄ tetragonal nanosheets（TNSs）,which could effectively accumulate in the tumor under magnetic targeting,whilst gradually transforming to small particles（⁵ nm）over three weeks.These were then effectively excreted from the body after exerting their therapeutic effect.The aqueous dispersion of PVP coated Fe₃S₄ TNSs had an intense near-infrared absorption,excellent photothermal conversion efficiency（64.3%）and great T₂ weighted magnetic resonance imaging properties(71.3 mM^-1S^-1).In addition,Fe₃S₄ TNSs could realize a synergistic photothermal therapy（PTT）/chemodynamic therapy（CDT）,because the localized heat produced by PTT from the defect-rich structure could enhance the Fenton process by utilizing the overproduced H₂O₂ in the tumor microenvironment,and in return,the produced·OH could inhibit tumor growth and recurrence after PPT.（3）High-efficiency and safe sulfur doped iron oxides for for magnetic resonance imaging guided photothermal/magnetic hyperthermia therapyWe report on one-pot hydrothermal strategy to synthesize water-dispersible sulfur doped iron oxides（SDIO）with different phase structure and explore the relation between different SDIO and their induction heating capacities as a guideline to obtain the optimal photo-magnetic hyperthermia agents.The aqueous dispersion exhibits good biocompatible,excellent photothermal conversion efficiency（55.8%）and great T₂weighted magnetic resonance imaging(63.7 mM^-1 s^-1).Significantly,in in vivo studies,SDIO exhibit additive therapeutic effect to effectively eliminate the tumour under a biological safe range of AC magnetic field(H·f=4.3<5.0×10⁶ kA m^-1 s^-1)and an 808 nm laser irradiation at the safe density of 0.33 W cm^-2 and can be chiefly metabolized from the body after one month.This work may provide a further exploration in the thermotherapeutic research.