Holmium (Iii)-Doped Multifunctional Nanotheranostic Agent for Ultra-High-field Magnetic Resonance Imaging-Guided Chemo-Photothermal Tumor Therapy

Ultra -high -field (UHF) MRI has shown great advantages over low -field magnetic resonance imaging (MRI). Despite being the most commonly used MRI contrast agents, gadolinium chelates perform poorly in high magnetic fields, which significantly weakens their T 1 intensity. In comparison, the rare element Holmium (Ho) -based nanoparticles (NPs) have demonstrated great potential as T 2 -weighted MRI contrast agents in UHF MRI due to their extremely short electron relaxation times (similar to 10 -13s). In this study, a multifunctional nanotherapeutic probe was designed for UHF MRI-guided chemotherapy and photothermal therapy. The Ho (III) -doped mesoporous polydopamine (Ho-MPDA, HM) nanosphere was loaded with the chemotherapeutic drug mitoxantrone (MTO) and then coated with 4T1 cell membranes to enhance active targeting delivery to breast cancer. The prepared nanotherapeutic probe MTO@HMM@4T1 (HMM@T) exhibited good biocompatibility, high drug -loading capability and great potential as Ho (III) -based UHF MRI contrast agents. Moreover, the biodegradation of HMM@T in response to the intratumor pH and glutathione (GSH) promotes MTO release. Near -infrared (NIR) light irradiation of HM induced photothermal therapy and further enhanced drug release. Consequently, HMM@T effectively acted as an MRI-guided tumor -targeting chemo-photothermal therapy against 4T1 breast cancer. Statement of significance Ultra -high -field (UHF) MRI has shown great advantages over low -field magnetic resonance imaging (MRI). Although gadolinium chelates are the most commonly used MRI contrast agents in clinical practice, they exhibit a significantly decreased T 1 relaxivity at UHF. Holmium exhibits outstanding UHF magnetic resonance capabilities in comparison with gadolinium chelates currently used in clinic. Herein, a theranostic nanodrug (HMM@T) was designed for UHF MRI-guided chemo-photothermal therapy. The nanodrug possessed remarkable UHF T 2 MRI properties (r 2 = 152.13 mM -1 s -1) and high drug loading capability of 18.4 %. The biodegradation of HMM@T NPs under triple stimulations of pH, GSH, and NIR led to an efficient release of MTO in tumor microenvironment. Our results revealed the potential of a novel UHF MRI-guided multifunctional nanosystem in cancer treatment. (c) 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.