TY - JOUR
T1 - Redox-Responsive Functional Iron Oxide Nanocrystals for Magnetic Resonance Imaging-Guided Tumor Hyperthermia Therapy and Heat-Mediated Immune Activation
AU - Li, Yao
AU - Ma, Xiaotu
AU - Liu, Xiaoli
AU - Yue, Yale
AU - Cheng, Keman
AU - Zhang, Qiang
AU - Nie, Guangjun
AU - Zhao, Xiao
AU - Ren, Lei
N1 - Funding Information:
L.R. acknowledges the support from National Natural Science Foundation of China (31870994 and U1904206) and the “Double-First Class” Foundation of Materials and Intelligent Manufacturing Discipline of Xiamen University. X.Z. acknowledges the support from the National Natural Science Foundation of China (31800838 and 32171384), the CAS Project for Young Scientists in Basic Research (YSBR-010), the Beijing Natural Science Foundation of China (Z200020), and the Beijing Nova Program (Z201100006820031).
Publisher Copyright:
© 2022 American Chemical Society. All rights reserved.
PY - 2022/3/25
Y1 - 2022/3/25
N2 - Magnetic nanoparticle-mediated mild hyperthermia is an emerging approach for tumor treatment and antitumor immune activation. However, the precise delivery of magnetic hyperthermia nanoagents inside tumor for mild magnetic hyperthermia therapy (MHT) via intravenous administration remains challenging. In this study, we developed a tumor microenvironment (TME)-responsive nanosystem based on cleavable methoxypolyethene glycol (mPEG) and transactivator of transcription (TAT) cell-penetrating peptide dual-decorated Fe3O4nanocrystals (mPEG@TAT@Fe3O4) and utilized it to facilitate effective magnetic resonance (MR) imaging, tumor MHT, and mild heat-mediated immune stimulation. The as-constructed mPEG@TAT@Fe3O4exhibited supreme sensitivity to the reducing environment in the TME for detaching the mPEG shell and strongly inhibited the proliferation of tumor cells with exposure to an alternating magnetic field. In vivo experiments in CT26 tumor-bearing mice showed that this nanodelivery system received an enhanced T2-weighted MR imaging-guided tumor MHT by achieving an 85.5% tumor inhibition rate and induced a magnetic hyperthermia-immune synergistic therapy. Notably, the structure-variable delivery system showed a lower intravenous dosage than previously reported agents at a temperature of 43-44 °C induced by MHT. Together with no obvious agent-related adverse events, our study successfully prepared a promising systemic delivery nanomedicine for MR imaging-guided tumor-targeting MHT and provided an attractive method to turn "cold" tumor to "hot".
AB - Magnetic nanoparticle-mediated mild hyperthermia is an emerging approach for tumor treatment and antitumor immune activation. However, the precise delivery of magnetic hyperthermia nanoagents inside tumor for mild magnetic hyperthermia therapy (MHT) via intravenous administration remains challenging. In this study, we developed a tumor microenvironment (TME)-responsive nanosystem based on cleavable methoxypolyethene glycol (mPEG) and transactivator of transcription (TAT) cell-penetrating peptide dual-decorated Fe3O4nanocrystals (mPEG@TAT@Fe3O4) and utilized it to facilitate effective magnetic resonance (MR) imaging, tumor MHT, and mild heat-mediated immune stimulation. The as-constructed mPEG@TAT@Fe3O4exhibited supreme sensitivity to the reducing environment in the TME for detaching the mPEG shell and strongly inhibited the proliferation of tumor cells with exposure to an alternating magnetic field. In vivo experiments in CT26 tumor-bearing mice showed that this nanodelivery system received an enhanced T2-weighted MR imaging-guided tumor MHT by achieving an 85.5% tumor inhibition rate and induced a magnetic hyperthermia-immune synergistic therapy. Notably, the structure-variable delivery system showed a lower intravenous dosage than previously reported agents at a temperature of 43-44 °C induced by MHT. Together with no obvious agent-related adverse events, our study successfully prepared a promising systemic delivery nanomedicine for MR imaging-guided tumor-targeting MHT and provided an attractive method to turn "cold" tumor to "hot".
KW - immune activation
KW - iron oxide nanoparticles
KW - magnetic hyperthermia therapy
KW - magnetic resonance imaging
KW - redox responsive
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U2 - 10.1021/acsanm.2c00898
DO - 10.1021/acsanm.2c00898
M3 - Article
AN - SCOPUS:85127310542
VL - 5
SP - 4537
EP - 4549
JO - ACS Applied Nano Materials
JF - ACS Applied Nano Materials
SN - 2574-0970
IS - 3
ER -