MnCO(3)-mineralized polydopamine nanoparticles as an activatable theranostic agent for dual-modality imaging-guided photothermal therapy of cancers

Background: 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. Methods: Cellular uptake, cytotoxicity assay, and in vitro photothermal conversion efficiency of MnCO(3)-mineralized fluorescent polydopamine nanoparticles (MnCO(3)-FPNPs) were evaluated using 4T1 breast cancer cells. In vivo 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/cm(2)) for 10 min, measuring the size of the tumors every 2 days. Results: At physiological pH (7.4), MnCO(3)-FPNP is efficiently quenched. Conversely, at acidic pH (5.4), the strong fluorescence (FL) is recovered due to the dissociation of Mn(2+) from the FPNPs. At pH 7.4, MnCO(3)-FPNP activity is silenced to enhance water proton relaxation due to unionized MnCO(3) maintenance; conversely, at acidic pH (5.4), MnCO(3)-FPNPs efficiently release Mn(2+) ions, thereby resulting in T(1)-weighted magnetic resonance (MR) contrast enhancement. MnCO(3)-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. Conclusions: Our studies exhibited unique “OFF-ON” activation abilities in FL/MR dual imaging and PTT functions. This approach suggests that the MnCO(3)-FPNPs may serve as a useful platform for various mineralization-based multimodal imaging-guided PTT models for many cancer theranostic applications.