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

Abstract

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-Fe ₃O ₄, 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.