Dual-Target Multifunctional Superparamagnetic Cationic Nanoliposomes for Multimodal Imaging-Guided Synergistic Photothermal/Photodynamic Therapy of Retinoblastoma.

Background: With high malignancy, retinoblastoma (RB) commonly occurs in infants and has incredible difficulty with the early diagnosis. In recent years, the integrated theranostics of multimodal imaging-guided therapy has shown promising potential for oncotherapy. Purpose: To prepare folate/magnetic dual-target theranostic nanoparticles integrating with US/PA/MR imaging and the synergistic photothermal treatment (PTT)/photodynamic treatment (PDT) for the early diagnosis and timely intervention of RB cancer. Methods: Folate/magnetic dual-target cationic nanoliposomes (CN) encapsulating indocyanine green (ICG) and perfluorohexane(PFH)(FA-CN-PFH-ICG-Fe3O4, FCNPIFE) were synthesized and characterized. Then we evaluated their targeting ability, US/PA/MR imaging effects, and the efficacy of synergistic PTT/PDT in vitro and in vivo. Finally, we explored the mechanism of synergistic PTT/PDT in Y79 tumor-bearing mice. Results: FCNPIFEs were stable and uniform in 7 days. They showed excellent in vitro targeting ability with a 95.29% cell uptake rate. The in vitro US/PA/MRI imaging results of FCNPIFEs showed a concentration-dependent manner, and in vitro therapy FCNPIFEs exhibited an enhanced anticancer efficacy against Y79 cells. In vivo analysis confirmed that FCNPIFEs enabled a targeted synergistic PTT/PDT under US/PA/MR imaging guidance in Y79 tumor-bearing mice, achieving almost complete tumor regression. Immunofluorescence results displayed weaker fluorescence intensity compared with other single treatment groups, confirming that PTT/PDT synergistic therapy effect was achieved by down-regulating the expression of HIF-1α and HSP70. Conclusion: FCNPIFEs were verified as promising theranostic nanoliposomes for RB oncotherapy and showed great potential in clinical application.

Multimodal imaging and photothermal synergistic immunotherapy of retinoblastoma with tuftsin-loaded carbonized MOF nanoparticles.

Retinoblastoma (Rb) represents 3% of all childhood malignancies and seriously endangers children's lives and quality of life. Early diagnosis and treatment can save children's vision as much as possible. Multifunctional nanoparticles have become a research hotspot in recent years and are expected to realize the integration of early diagnosis and early treatment. Therefore, we report a nanoparticle with dual-mode imaging, photothermal therapy, and immune activation: carbonized MOF nanoparticles (CM NPs) loaded with the immune polypeptide tuftsin (CMT NPs). The dual-mode imaging ability, antitumor effect, and macrophage immunity activation ability of these nanoparticles combined with laser irradiation were studied. The biosafety of CMT NPs was detected. The multifunctional magnetic nanoparticles enhanced photoacoustic (PA) and magnetic resonance (MR) imaging in vivo and in vitro, facilitating diagnosis and efficacy evaluation. The combined effect of CMT NPs and laser irradiation was recorded and verified. Through the accumulation of magnetic field nanoparticles in tumors, the photothermal conversion of nanoparticles under laser irradiation led directly to tumor apoptosis/necrosis, and the release of tuftsin induced macrophage M1-type activation, resulting in antitumor immune effects. Enhanced PA/MR imaging CMT NPs have great potential in dual-mode image-guided laser/immune cotherapy. The nanoparticles have high biosafety and have potential in cancer treatment.

Biophysical characterization and in vitro imaging of carbonized MOFs.

Nanoparticles have been widely used in biological imaging and treatments of various diseases, especially for studies of tumors, due to their high efficiency in drug delivery and many other functions. Metal-organic frameworks have been an important research area in recent years because of advantages such as large apertures, adjustable structural compositions, adjustable sizes, multifunctionality, high drug loading, good biocompatibility and so on, and they show promise as multifunctional drug carriers. In this study, a carbonized MOF with photothermal therapeutic potential and dual-mode imaging capability was prepared. The biophysical properties of MIL-100 and C-MIL nanoparticles were determined, such as particle size, zeta potential and saturation magnetization strength. CCK-8 cell assays and mouse HE sections confirmed that C-MIL nanoparticles have good in vitro and in vivo biocompatibility. The solution temperature of C-MIL nanoparticles reached 58.1 °C during sustained laser irradiation at 808 nm, which confirmed the photothermal potential of the nanoparticles. Moreover, in biological imaging, C-MIL nanoparticles showed the ability to support in vitro nuclear magnetic and photoacoustic dual-mode imaging. C-MIL nanoparticles provide new options for tumor therapy, drug delivery and biological imaging.

Mesoporous composite nanoparticles for dual-modality ultrasound/magnetic resonance imaging and synergistic chemo-/thermotherapy against deep tumors.

High-intensity focused ultrasound (HIFU) is a promising and noninvasive treatment for solid tumors, which has been explored for potential clinical applications. However, the clinical applications of HIFU for large and deep tumors such as hepatocellular carcinoma (HCC) are severely limited by unsatisfactory imaging guidance, long therapeutic times, and damage to normal tissue around the tumor due to the high power applied. In this study, we developed doxorubicin/perfluorohexane-encapsulated hollow mesoporous Prussian blue nanoparticles (HMPBs-DOX/PFH) as theranostic agents, which can effectively guide HIFU therapy and enhance its therapeutic effects in combination with chemotherapy, by decreasing the cavitation threshold. We investigated the effects of this agent on ultrasound and magnetic resonance imaging in vitro and in vivo. In addition, we showed a highly efficient HIFU therapeutic effect against HCC tumors, as well as controlled drug release, owing to the phase-transitional performance of the PFH. We therefore conclude that HMPB-DOX/PFH is a safe and efficient nanoplatform, which holds significant promise for cancer theranostics against deep tumors in clinical settings.