Multifunctional Prussian blue-based nanomaterials: Preparation, modification, and theranostic applications

Prussian blue (PB) is an USA Food and Drug Administration (U.S. FDA)-approved antidote for the treatment of radioactive element poisoning such as thallium, which has been proved to have outstanding biosafety. Controllable morphology, size and structure of PB-based nanomaterials (PB NMs), and their excellent physicochemical properties, make them play an important role in the biomedical fields, such as drug delivery nano-systems, molecular imaging, and cancer treatment. In recent years, PB NMs have made great progress in cancer theranostics. Therefore, it is a great urgent to systematically summarize the recent progress to better serve the broad community of researchers. This review begins with the synthesis methods, regulatory approaches, and modification methods of PB NMs to achieve more uniform size and morphology. Next, according to the different properties of PB NMs, its application in the cancer theranostics has been gradually expanded, mainly including PB NMs for cancer imaging (single-modal and multi-modal imaging) and cancer therapy (monotherapy and combination therapy). For cancer imaging, single-modal imaging (e.g., photoacoustic (PA) imaging, ultrasound (US) imaging, magnetic resonance (MR) imaging), and multi-modal imaging based on PB NMs are systematically summarized, as well as strategies to improve the diagnostic effectiveness. For monotherapy, PB NMs are extensively used in photothermal therapy (PTT), sonodynamic therapy (SDT), and photodynamic therapy (PDT), owing to their excellent photothermal performance and unique physicochemical properties. Combined cancer therapy based on PB NMs to further enhance the cancer-killing efficiency is also systematically summarized. Moreover, the in vivo long-term toxicity of PB NMs is emphasized. Finally, the challenges, key factors, and the future prospects in the clinical transformation of PB NMs as multifunctional theranostic agents are simultaneously discussed. This review will provide reference and guidance for the design and application of PB NMs in the future bioapplications.