Size-Tunable Gd(2)O(3)@Albumin Nanoparticles Conjugating Chlorin e6 for Magnetic Resonance Imaging-Guided Photo-Induced Therapy

尺寸可调的Gd(2)O(3)@白蛋白纳米粒子偶联氯e6用于磁共振成像引导的光诱导治疗

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Abstract

Protein nanoparticles as nanocarriers are of particular interest in the field of cancer therapy. Nevertheless, so far a facile fabrication of theranostic protein nanoparticles have been explored with limited success for cancer imaging and therapy. In this work, we demonstrate the controllable synthesis of size-tunable Gd(2)O(3)@albumin conjugating photosensitizer (PS) (GA-NPs) using hollow albumin as the nanoreactor for magnetic resonance imaging (MRI)-guided photo-induced therapy. The growth of Gd(2)O(3) nanocrystals within the hollow nanoreactors is well regulated through reaction time, and a typical PS (e.g. chlorin e6) is further conjugated with the protein corona of the nanoreactor through facile chemical coupling, followed by the formation of theranostic GA-NPs. GA-NPs exhibit good longitudinal relaxivity, ideal photostability, enhanced cellular uptakes, and preferable size-dependent tumor accumulation. Moreover, GA-NPs effectively generate remarkable photothermal effect, intracellular reactive oxygen species from Ce6, and subsequent cytoplasmic drug translocation, thereby leading to severe synergistic photothermal and photodynamic cell damages. Consequently, GA-NPs exhibit an in vivo size-dependent MRI capacity with enhanced imaging contrast for effective tumor localization, and also generate a potent synergistic photodynamic therapy/photothermal therapy efficacy under irradiation owing to their enhanced tumor accumulation and strong photo-induced cytotoxicity. These results suggest that GA-NPs can act as a promising theranostic protein nanoplatform for cancer imaging and photo-induced therapy.

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