Multifunctional liposome for photoacoustic/ultrasound imaging-guided chemo/photothermal retinoblastoma therapy

Abstract

Retinoblastoma (RB) is a malignant intraocular neoplasm that occurs in children. Diagnosis and therapy are frequently delayed, often leading to metastasis, which necessitates effective imaging and treatment. In recent years, the use of nanoplatforms allowing both imaging and targeted treatment has attracted much attention. Herein, we report a novel nanoplatform folate-receptor (FR) targeted laser-activatable liposome termed FA-DOX-ICG-PFP@Lip, which is loaded with doxorubicin (DOX)/indocyanine green (ICG) and liquid perfluoropentane (PFP) for photoacoustic/ultrasound (PA/US) dual-modal imaging-guided chemo/photothermal RB therapy. The dual-modal imaging capability, photothermal conversion under laser irradiation, biocompatibility, and antitumor ability of these liposomes were appraised. The multifunctional liposome showed a good tumor targeting ability and was efficacious as a dual-modality contrast agent both in vivo and in vitro . When laser-irradiated, the liposome converted light energy to heat. This action caused immediate destruction of tumor cells, while simultaneously initiating PFP phase transformation to release DOX, resulting in both photothermal and chemotherapeutic antitumor effects. Notably, the FA-DOX-ICG-PFP@Lip showed good biocompatibility and no systemic toxicity was observed after laser irradiation in RB tumor-bearing mice. Hence, the FA-DOX-ICG-PFP@Lip shows great promise for dual-modal imaging-guided chemo/photothermal therapy, and may have significant value for diagnosing and treating RB.

Looking deep inside tissue with photoacoustic molecular probes: a review

“…However, materials are also designed such that a single multimodal agent can work for different imaging systems simultaneously. PAI has been combined with various other imaging modalities, such as MRI, 180 , 258 – 260 US imaging, 100 , 101 , 261 fluorescence, 262 – 265 PET, 206 surface-enhanced Raman scattering (SERS), 172 , 232 , 266 OCT, 267 , 268 and two-photon microscopy 269 . At the same time, multimodal contrast agents have also been developed to work in sync with these multimodal imaging systems.…”

“…However, the unsatisfactory results of a single therapeutic treatment prompted attention to the development of combination therapy, such as PTT and chemotherapy, 101 , 262 , 293 PDT and chemotherapy, 294 and PTT and PDT. 258 , 259 , 288 , 295 FA-DOX-ICG-PFP@Lip was proposed as a laser-triggered contrast agent that targets retinoblastoma and, moreover, ablates tumor and helps drug delivery under laser excitation.…”

“… 258 , 259 , 288 , 295 FA-DOX-ICG-PFP@Lip was proposed as a laser-triggered contrast agent that targets retinoblastoma and, moreover, ablates tumor and helps drug delivery under laser excitation. 101 As a folate-receptor targeted laser-activatable liposome, FA-DOX-ICG-PFP@Lip was a PA/US dual-modal contrast agent, loaded with doxorubicin, ICG, and liquid perfluoropentane. It could also be used in imaging-guided chemo/photothermal retinoblastoma (RB) therapy.…”

“…Hence, multimodal probes have also been developed to aid such imaging/therapeutic systems. 101 – 108 …”

Advances in biomaterials for the treatment of retinoblastoma

“…Very recently, in 2022, multifunctional liposome for photoacoustic/ultrasound imaging-guided chemo/photothermal retinoblastoma therapy was reported. 298 Nanoplatform folate-receptor (FR) targeted laser-activatable liposome termed FA-DOX-ICG-PFP@Lip, which is loaded with doxorubicin (DOX)/indocyanine green (ICG) and liquid perfluoropentane (PFP) for photoacoustic/ ultrasound (PA/US) dual-modal imaging-guided chemo/photothermal retinoblastoma treatment was synthesized and characterized (Fig. 10B).…”