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.

Advances in Prostate‐Specific Membrane Antigen (PSMA)‐Targeted Phototheranostics of Prostate Cancer

“…Fluorescence imaging devices equipped with the da Vinci surgical robot established the foundation for the clinical translation of near-infrared fluorescenceguided tumor resection. In addition, the widespread and high expression of PSMA receptors in PCa cells itself holds high [79] Copyright 2021, Wiley-VCH.…”

“…[ 78 ] Recently, Hua Zhu and Zhi Yang et al used melanin nanoparticles as carriers by adsorbing them on paramagnetic metal ions (Mn 2+ ), labeling them with radionuclides ( 89 Zr and 131 I), and finally conjugating them to highly specific PSMA‐targeted small‐molecule inhibitors on its surface to construct a structurally stable PCa‐specific probe, PMNs‐II‐813, for the integration of multiplex enhanced diagnosis and treatment (PET, MRI, PAI, and PTT) ( Figure A–C). [ 79 ] Melanin nanoparticles can be used for PAI and PTT; the paramagnetic metal ions Mn 2+ and positron nuclide 89 Zr are used for constructing PET and T 1 ‐weighted MRI, respectively; and the radionuclide 131 I provides radioisotope therapy (RIT) capability to the probe. In terms of imaging, the fusion of PET and MRI empowers the nanoprobe to monitor intratumoral distribution and therapeutic effects in real time for >7 days.…”

“…D-F) Dual therapy (PTT and RIT) with PMNs-II-813 showed the best therapeutic effect. Reproduced with permission [79]. Copyright 2021, Wiley-VCH.…”

Advances of Nanomedicine in Radiotherapy

“…This melanin nanoprobe could have two therapeutic functions: PTT and RIT, when labeled with 131 I. In the mouse model of prostate cancer, combined treatment of PTT and RIT produced a significantly better tumor-suppressive effect than the single treatment model [64].…”

Application Analysis of 124I-PPMN for Enhanced Retention in Tumors of Prostate Cancer Xenograft Mice

“… 16 Organic melanin nanoparticles (MNPs) are constructed from bioderived melanin and exhibit high safety and biocompatibility. 17 , 18 This type of nanoparticle has been used as a carrier of chemotherapeutic drugs by binding drugs through π-π stacking interactions because of the abundant aromatic rings or hydrogen-bonding groups on its surface. 19 MNPs have controllable particle size, stable structure, good biocompatibility and biodegradability.…”