Given that cancer mortality is usually due to a late diagnosis, early detection is crucial to improve the patient’s results and prevent cancer-related death. Imaging technology based on novel nanomaterials has attracted much attention for early-stage cancer diagnosis. In this study, a new block copolymer, poly(ethylene glycol)-poly(l-lactide) diblock copolymer (PEG-PLLA), was synthesized by the ring-opening polymerization method and thoroughly characterized using Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance spectroscopy (H-NMR), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). The obtained PEG-PLLA was used to prepare nanoparticles encapsulated with perfluoropentane and salicylic acid by the emulsion-solvent evaporation method, resulting in a new dual-mode nano-image probe (PEG-PLLA@SA·PFP). The zeta potential and mean diameter of the obtained nanoparticles were measured using dynamic light scattering (DLS) with a Malvern Zetersizer Nano. The in vitro biocompatibility of the PEG-PLLA nanoparticles was evaluated with cell migration, hemolysis, and cytotoxicity assays. Ultrasonic imaging was performed using an ultrasonic imaging apparatus, and chemical exchange saturation transfer (CEST) MRI was conducted on a 7.0 T animal scanner. The results of IR and NMR confirmed that the PEG-PLLA was successfully synthesized. The particle size and negative charge of the nanoparticles were 223.8 ± 2.5 nm and −39.6 ± 1.9 mV, respectively. The polydispersity of the diameter was 0.153 ± 0.020. These nanoparticles possessed good stability at 4 °C for about one month. The results of cytotoxicity, cell migration, and hemolysis assays showed that the carrier material was biocompatible. Finally, PEG-PLLA nanoparticles were able to significantly enhance the imaging effect of tumors by the irradiation of ultrasound and saturation by a radiofrequency pulse, respectively. In conclusion, these nanoparticles exhibit promising dual-mode capabilities for US/CEST MR imaging.

Background: Medical imaging modalities, such as magnetic resonance imaging (MRI), ultrasound, and fluorescence imaging, have gained widespread acceptance in clinical practice for tumor diagnosis. Each imaging modality has its own unique principles, advantages, and limitations, thus necessitating a multimodal approach for a comprehensive disease understanding of the disease process. To enhance diagnostic precision, physicians frequently integrate data from multiple imaging modalities, driving research advancements in multimodal imaging technology research. Methods: In this study, hematoporphyrin-poly (lactic acid) (HP-PLLA) polymer was prepared via ring-opening polymerization and thoroughly characterized using FT-IR, ¹H-NMR, XRD, and TGA. HP-PLLA based nanoparticles encapsulating perfluoropentane (PFP) and salicylic acid were prepared via emulsion-solvent evaporation. Zeta potential and mean diameter were assessed using DLS and TEM. Biocompatibility was evaluated via cell migration, hemolysis, and cytotoxicity assays. Ultrasonic imaging was performed with a dedicated apparatus, while CEST MRI was conducted using a 7.0 T animal scanner. Results: We designed and prepared a novel dual-mode nanoimaging probe SA/PFP@HP-PLLA NPs. PFP enhanced US imaging, while salicylic acid bolstered CEST imaging. With an average size of 74.43 ± 1.12 nm, a polydispersity index of 0.175 ± 0.015, and a surface zeta potential of − 64.1 ± 2.11 mV. These NPs exhibit excellent biocompatibility and stability. Both in vitro and in vivo experiments confirmed the SA/PFP@HP-PLLA NP’s ability to improve tumor characterization and diagnostic precision. Conclusion: The SA/PFP@HP-PLLA NPs demonstrate promising dual-modality imaging capabilities, indicating their potential for preclinical and clinical use as a contrast agent.

The development of contrast agents that can be activated by multiple modes is of great significance for tumor diagnosis. In this study, the lactoferrin (Lf)-conjugated polylactic acid (PLLA) nanobubbles (Lf-PLLA NBs) were used to encapsulate liquid perfluoropentane (PFP) with the double emulsion method, creating PFP loaded (PFP/Lf-PLLA) NBs for the ultrasound/magnetic resonance dual-modality imaging of subcutaneous tumor. The particle diameter and stability of nanobubbles were investigated by photon correlation spectroscopy. The biocompatibility of nanobubbles was preliminarily evaluated by cell proliferation and migration assay, hemolysis rate, and blood biochemistry analysis. A B-mode clinical ultrasound real-time imaging system was used to perform ultrasonic imaging in vivo. Magnetic resonance imaging in vivo was applied with a clinical 3.0 T magnetic resonance imaging (MRI) scanner system. The mean particle diameter of PFP/Lf-PLLA NBs was 320.2 ± 4.1 nm with a low polydispersity index (PDI, 0.145 ± 0.025), and the NBs were negatively charged (−11.4 ± 0.4 mV). The transmission electron microscopy (TEM) results showed that PFP/Lf-PLLA NBs exhibited highly monodispersed and possessed an obvious spherical structure of nanocapsules. Nanobubbles had good stability at 4°C. Different concentrations of the PFP/Lf-PLLA NBs solution had no effect on the cell in cytotoxicity and cell migration, and the results of hemolysis rate and blood biochemistry assay also indicated the good biocompatibility of NBs. On the ultrasound/magnetic resonance imaging of tumor-bearing mice, PFP/Lf-PLLA NBs showed significantly enhanced contrast ability of tumor tissue. Therefore, PFP/Lf-PLLA NBs had great potential to be a contrast agent for tumor dual-modality imaging in vivo.

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