A Highly Specific Multiple Enhancement Theranostic Nanoprobe for PET/MRI/PAI Image‐Guided Radioisotope Combined Photothermal Therapy in Prostate Cancer

Abstract An integrated molecular probe for combined tumor‐targeted multimodal imaging and therapy in the era of precision medicine requires a multiplexed platform that simultaneously has high targeting specificity, versatile conjugation capability, and biocompatibility. Here, a novel biocompatible melanin nanoprobe (PMNs‐II‐813) coupled with a highly specific prostate‐specific membrane antigen small molecule inhibitor is developed for the targeted multimodal diagnosis and treatment of prostate cancer. The melanin nanoparticles demonstrate photoacoustic imaging and photothermal therapy (PTT) functionalities via strong near‐infrared absorption. The imaging contrast agents 89 Zr and Mn 2+ are stably conjugated to the nanoparticles for positron emission tomography (PET) and magnetic resonance imaging (MRI). Fusion PET/MRI with PMNs‐II‐813 enables the monitoring of treatment effects in real time and lasts for more than 1 week, demonstrating the capability for multimodal theranostics in prostate cancer. Labeling with a therapeutic radionuclide, 131 I, simultaneously endows the nanoprobe with the capability for radioisotope therapy (RIT) and PTT under triple‐modal imaging guidance. Combined PTT and RIT has an inhibitory effect on prostate cancer growth (tumor inhibition rate of ≈93% 20 days after treatment), which is significantly better than that with the single treatment. Overall, it is believed that PMNs‐II‐813 has potential for clinical translation to treat prostate cancer.