Developing Smart Nanoparticles Responsive to the Tumor Micro-Environment for Enhanced Synergism of Thermo-Chemotherapy With PA/MR Bimodal Imaging

Abstract

With the development of nanotechnology, a theranostics nanoplatform can have broad applications in multimodal image-guided combination treatment in cancer precision medicine. To overcome the limitations of a single diagnostic imaging mode and a single chemotherapeutic approach, we intend to combat tumor growth and provide therapeutic interventions by integrating multimodal imaging capabilities and effective combination therapies on an advanced platform. So, we have constructed IO@MnO2@DOX (IMD) hybrid nanoparticles composed of superparamagnetic iron oxide (IO), manganese dioxide (MnO2), and doxorubicin (DOX). The nano-platform could achieve efficient T2-T1 magnetic resonance (MR) imaging, switchable photoacoustic (PA) imaging, and tumor microenvironment (TME)-responsive DOX release and achieve enhanced synergism of magnetic hyperthermia and chemotherapy with PA/MR bimodal imaging. The results show that IMD has excellent heating properties when exposed to an alternating magnetic field (AMF). Therefore, it can be used as an inducer for tumor synergism therapy with chemotherapy and hyperthermia. In the TME, the IMD nanoparticle was degraded, accompanied by DOX release. Moreover, in vivo experimental results show that the smart nanoparticles had excellent T2-T1 MR and PA imaging capabilities and an excellent synergistic effect of magnetic hyperthermia and chemotherapy. IMD nanoparticles could significantly inhibit tumor growth in tumor-bearing mice with negligible side effects. In conclusion, smart IMD nanoparticles have the potential for tumor diagnosis and growth inhibition as integrated diagnostic nanoprobes.

Advances in nanotechnology-based targeted-contrast agents for computed tomography and magnetic resonance

“…Hollow nanoplatforms based on manganese (Mn), a metallic element paramagnetic in nature, are currently receiving significant attention in the field of MR-enhanced imaging contrast agents and diagnostic-therapeutic integrated platforms. 38 These platforms provide the advantages of both the hollow structures and the intrinsic diagnostic and therapeutic properties of Mn2 + . Empty spaces in particular can contain various small-molecule medications.…”

“…Danafar et al 37 Superparamagnetic substances can decrease T2 relaxation time and boost a low T2 signal to a certain degree. Luo et al 38 created a nanoplatform consisting of IO@MnO 2 @DOX (IMD) hybrid NPs composed of superparamagnetic IO (SPION), manganese dioxide (MnO 2 ), and doxorubicin (DOX). They found that its use allows efficient T2-weighted MRI and switchable photoacoustic (PA) imaging.…”

“…3 Nano-formulations have garnered significant attention in basic research into disease diagnosis and treatment owing to their unique properties, including enhanced permeability and retention (EPR) in solid tumors and surface modifiability. 4–47 Research into the development of more targeted nano-enhanced contrast agents aims to combine the potential advantages of nanomaterials to overcome the shortcomings of traditional small-molecule contrast agents, such as rapid metabolism and poor targeting. Improvement of the diagnostic ability and level of medical imaging has become an important research area in the preparation of medical imaging-enhanced contrast agents.…”

Targeting and repolarizing M2-like tumor-associated macrophage-mediated MR imaging and tumor immunotherapy by biomimetic nanoparticles

“…In recent years, it has been found that manganese dioxide nanoparticles (MDN) has good biocompatibility, adjustable structure, ability to carry drugs, and the ability to react with GSH or H 2 O 2 to reduce Mn 4+ to Mn 2+ . The resulting Mn 2+ enhances the ability of T1-weighted MRI [ 18 ] [ 19 ] [ 20 ]. Most of the previously reported MDN are nano-flake and particle structure, which may not be ideal for drug loading and effective release [ 21 ] [ 22 ].…”

Multifunctional Nanosnowflakes for T1-T2 Double-Contrast Enhanced MRI and PAI Guided Oxygen Self-Supplementing Effective Anti-Tumor Therapy

“…[25][26][27][28] Our group also reported a MnO 2based TME-responsive nanoprobe for multimodal imaging. 29 However, most of the reported MnO 2 nanostructures were nanosheets or nanocomposites combined with other nanoparticles, which might not achieve the desired drug-loading effect. 30,31 Therefore, the development of structures with large specific surface areas, robust structures, and sufficient drugloading capacity remains a top priority.…”