Mn-Doped Nano-Hydroxyapatites as Theranostic Agents with Tumor pH-Amplified MRI-Signal Capabilities for Guiding Photothermal Therapy

Chengyu Li, Ziyou Ding, Yingchao Han State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Biomedical Materials and Engineering Research Center of Hubei Province, Wuhan University of Technology, Wuhan, 430070, People’s Republic of ChinaCorrespondence: Yingchao Han, Email hanyingchao@whut.comBackground: The integration of diagnostic and therapeutic functions into a biosafe nanoplatform with intelligent response functions at the tumor microenvironment (TME) is a promising strategy for cancer therapy.Methods: Mn-doped nano-hydroxyapatite (nHAPMn) nanoparticles were successfully prepared via a simple coprecipitation method for magnetic resonance imaging (MRI)-guided photothermal therapy. This study is the first to report on the use of Mn to render biodegradable hydroxyapatite suitable for MRI and effective photothermal therapy (PTT) simultaneously by regulating the pH of nHAPMn during the preparation process.Results: Combined with near-infrared (NIR) laser irradiation, a photothermal conversion efficiency of 26% and effective photothermal lethality in vitro were achieved. Moreover, the degradation of nHAPMn led to the release of Mn ions and amplified the MRI signals in an acidic TME, which confirmed that nHAPMn had a good pH-responsive MRI capacity in solid tumors. In animal experiments, tumors in the nHAPMn5+NIR group completely abated after 14 days of treatment, with no significant recurrence during the experiment.Conclusion: Therefore, nHAPMn is promising as a nanotheranostic agent and can be effective in clinical diagnosis and therapy for treating cancer.Graphical Abstract: Keywords: photothermal therapy, magnetic resonance imaging, hydroxyapatite, manganese, pH-amplifie