Xi Zhou,Xiaolin Lv,Wen Zhao,Tiantian Zhou,Shupeng Zhang,Zhan Shi,Shefang Ye,Lei Ren,Zhiwei Chen
This study reports a multifunctional core/shell nanoparticle (NP) that can be used for amplified magnetic resonance image (MRI), enhanced photothermal therapy (PTT) and magnetic hyperthermia therapy (MHT) due to its surface coating with a porous shell. Importantly, by means of introducing the surface coating of a porous shell, it helps entrap large quantities of water around NPs and allow more efficient water exchange, leading to greatly improved MR contrast signals. Besides, the porous shell helps the near-infrared (NIR) absorbance of the core, and then the extremely enhanced thermal effect can be obtained under synergistic combination of PTT and MHT. By synthesizing multifunctional porous MnFe2O4/PB as an example, we found that the transversal relaxivity (r2) of MnFe2O4 NPs might improve from 112.11 to 123.46 mM−1 s−1, and the specific absorption rate (SAR) of MnFe2O4/PB nanoparticles reached unprecedented levels of up to 4800 W g−1 compared with the SAR 1182 W g−1 of PTT under an 808 nm laser and 180 W g−1 of MHT under an external AC magnetic field. Meanwhile, when MnFe2O4 was decorated on PB nanoparticles, the magnetic properties became lower slightly, but the synergistic photothermal/magnetic hyperthermia conversion was enhanced greatly. Subsequently, in vitro T1–T2 dual-modal MRI, PTT and MHT results verified that MnFe2O4/PB could serve as an excellent MRI/PTT/MHT theranostic agent. Furthermore, the MnFe2O4/PB NPs were applied as a T1–T2 dual-modal MRI, PTT and MHT theranostic agent for in vivo MRI-guided photothermal and magnetic hyperthermia ablation of tumors by intratumoral injection in 4T1 tumor-bearing mice. The T1–T2 dual-modal MR imaging result shows a significantly contrast in the tumor site. The MPB-mediated PTT and MHT result shows high therapeutic efficiency as a result of high photothermal and magnetic hyperthermia conversion efficiency. The multifunctional NPs have a great potential application for future clinical tumorous diagnosis and treatment.
To elevate the accurate diagnosis of tumors, nanomaterial-based magnetic resonance imaging (MRI) contrast agents are being rapidly developed. In this paper, we report the large-scale synthetic method of Fe3O4 nanoparticles by high-temperature thermal decomposition and their application as time-dependent T1–T2 dual-modal MRI contrast agents in rabbit hepatic tumors. The Fe3O4 nanoparticles are modified with bull serum albumin (BSA), which provides excellent biocompatibility and colloidal stability. These nanoparticles also exhibit a high r1 value of 6.99 mM–1 s–1 and a low r2 value of 24.11 mM–1 s–1 at a clinically relevant magnetic field (3.0 T). In in vivo experiments, after intravenous administration with these nanoparticles, the rapid T2-weighted effect can be acquired within 5 min and the slow T1 contrast enhancement at the tumor site appears at 90 min. The explanation of this phenomenon is possibly due to the different accumulation rates and states of the nanoparticles in different tissues. In normal liver tissue, the nanoparticles can be quickly phagocytosed by a reticuloendothelial system and accumulated in the liver. These accumulated nanoparticles aggregate, improving the T2-weighted effect and reducing the T1-weighted effect. However, because of an enhanced permeation and retention effect, the nanoparticles are delivered into tumor tissue gradually and dispersedly, which takes a longer time to generate the T1-weighted effect at the tumor site. In summary, these Fe3O4 nanoparticles have significant potential to improve the diagnostic accuracy and sensitivity in MRI.
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