MnCO₃-mineralized polydopamine nanoparticles as an activatable theranostic agent for dual-modality imaging-guided photothermal therapy of cancers

Abstract

<b>Background:</b> Single imaging modality is still insufficient to evaluate the biological and anatomical structures of tumors with high accuracy and reliability. Generation of non-specific contrast, leading to a low target-to-background signal ratio, results in low imaging resolution and accuracy. Tumor environment-specific activatable multifunctional contrast agents need to maximize the contrast signals, representing a dual imaging-guided photothermal therapy (PTT) at target tumor sites. <b>Methods:</b> Cellular uptake, cytotoxicity assay, and <i>in vitro</i> photothermal conversion efficiency of MnCO₃-mineralized fluorescent polydopamine nanoparticles (MnCO₃-FPNPs) were evaluated using 4T1 breast cancer cells. <i>In vivo</i> dual-modality imaging was performed using IVIS imaging and a 4.7 T animal MRI systems after injection into 4T1 tumor-bearing nude mice. The effects of photothermal therapeutic through PTT were measured after irradiation with an 808 nm laser (1.5 W/cm²) for 10 min, measuring the size of the tumors every 2 days. <b>Results:</b> At physiological pH (7.4), MnCO₃-FPNP is efficiently quenched. Conversely, at acidic pH (5.4), the strong fluorescence (FL) is recovered due to the dissociation of Mn²⁺ from the FPNPs. At pH 7.4, MnCO₃-FPNP activity is silenced to enhance water proton relaxation due to unionized MnCO₃ maintenance; conversely, at acidic pH (5.4), MnCO₃-FPNPs efficiently release Mn²⁺ ions, thereby resulting in <i>T</i> ₁-weighted magnetic resonance (MR) contrast enhancement. MnCO₃-FPNPs display a promising diagnostic ability for 4T1 breast cancer xenograft models, as well as exhibit a high photothermal conversion efficiency. A successful tumor treatment via their photothermal activity is accomplished within 14 days. <b>Conclusions:</b> Our studies exhibited unique "OFF-ON" activation abilities in FL/MR dual imaging and PTT functions. This approach suggests that the MnCO₃-FPNPs may serve as a useful platform for various mineralization-based multimodal imaging-guided PTT models for many cancer theranostic applications.