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 3 O 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.

Advancements in Nanosystems for Ocular Drug Delivery: A Focus on Pediatric Retinoblastoma

“…ROS produced by NPs containing PFH was 6.15 times higher than that produced by NPs in the absence of PFH. Furthermore, the in vivo performance of these nanoparticles in Y79-bearing mice showed the most optimal anti-cancer effect (p < 0.0001), as the presence of PFH allowed for the synergistic effect of PTT and PDT [81]. Mudigunda et al (2022) created Palbociclib (PCB) and near-infrared (NIR)-dye-loaded hybrid (PLGA and PCL) polymeric NPs (PNPs) for the combined PCB and PTT effect.…”

Polydopamine-Based Targeted Nanosystem for Chemo/Photothermal Therapy of Retinoblastoma in a Mouse Orthotopic Model

“…However, the few photothermal/chemotherapy studies that have been reported are mainly restricted to ectopic models involving subcutaneous implantation. 3 , 16–18 Orthotopic models, which closely mimic the biological characteristics of clinical tumors, are rarely featured in research to date. The primary distinction between subcutaneous and orthotopic animal models lies in the tumor microenvironment, impacting the tumor immune response and treatment outcomes.…”

“…(ii) The targeting FA ligand guided the NPs to specifically bind to folate receptors (FRs), which are specific markers on the surface of Rb cells. 16 , 17 , 22 The nanosized particles and morphology of the NPs concurrently mediate the process of phagocytosis, due to the enhanced permeability and retention (EPR) of nanomedicine. 23 , 24 (iii) Photothermal conversion facilitates the endosomal escape of nanodrugs, realizing synergistic effects.…”

Bioactive Polymeric Nanoparticles of Moringa oleifera Induced Phyto-Photothermal Sensitization for the Enhanced Therapy of Retinoblastoma

“…PTT employs plasmonic metallic nanosystems or NIR dye, which convert the incident NIR light into light, thereby causing a localized ablation of the tumor cells [ 18 , 19 , 20 ]. Several studies have reported the use of photothermal therapy for the treatment of retinoblastoma [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ]. However, recent literature reports reveal that the tumor cells acquire inherent resistance to the heat that is induced via PTT through the activation of heat shock proteins (HSP).…”