Manganese oxide nanoplatforms for disease diagnosis and treatment: Progress, challenges and opportunities

Progress in the development of manganese oxide nanoparticles (MONPs) has offered an alternative to the current Gd-based T1 magnetic resonance image (MRI) contrast agents for early-stage diagnosis of life-threatening dis-eases. MONPs also possess unique self-degradation characteristics, making them suitable for the therapeutic delivery of drugs and genes. Advances in the NP synthesis and characterisation, especially fundamental insights into the thermodynamically and kinetically controlled growth of NP and rich surface chemistry offering conjugation of biomolecules and polymers to its surface, have enabled the reproducible production of multi-functional targeted MONPs in various sizes and shapes. The integration of diagnosis and therapeutic capabilities within a single entity, so-called "nanotheranostics", has offered new hope for using them for simultaneous real-time monitoring of disease progression in response to the treatment, thus evaluating the efficacy of therapeutic treatment. In this review, we highlight the recent advancements in the synthesis of MONPs and functionalisation strategies used to realise their theranostic potential. We discuss the basic physics of MR imaging and factors influencing the contrast enhancement mechanism of MONPs and review the use of multifunctional MONPs for dual and multimodal imaging and therapeutic delivery applications. This review also discusses how the bio-logical properties of MONPs can influence their performance in a biological environment, including induced toxicity, which should be taken into consideration for designing next-generation engineered precision MONPs for disease diagnosis and treatment. Finally, we also provide a forward-looking perspective to accelerate the translation of MONPs into the clinical setting.