Liposomal IR-780 as a Highly Stable Nanotheranostic Agent for Improved Photothermal/Photodynamic Therapy of Brain Tumors by Convection-Enhanced Delivery

Abstract

As a hydrophobic photosensitizer, IR-780 suffers from poor water solubility and low photostability under near infrared (NIR) light, which severely limits its use during successive NIR laser-assisted photothermal/photodynamic therapy (PTT/PDT). To solve this problem, we fabricate cationic IR-780-loaded liposomes (ILs) by entrapping IR-780 within the lipid bilayer of liposomes. We demonstrate enhanced photostability of IR-780 in ILs with well-preserved photothermal response after three repeated NIR laser exposures, in contrast to the rapid decomposition of free IR-780. The cationic nature of ILs promotes fast endocytosis of liposomal IR-780 by U87MG human glioblastoma cells within 30 min. For PTT/PDT in vitro, ILs treatment plus NIR laser irradiation leads to overexpression of heat shock protein 70 and generation of intracellular reactive oxygen species by U87MG cells, resulting in enhanced cytotoxicity and higher cell apoptosis rate. Using intracranial glioma xenograft in nude mice and administration of ILs by convection enhanced delivery (CED) to overcome blood-brain barrier, liposomal IR-780 could be specifically delivered to the brain tumor, as demonstrated from fluorescence imaging. By providing a highly stable liposomal IR-780, ILs significantly improved anti-cancer efficacy in glioma treatment, as revealed from various diagnostic imaging tools and histological examination. Overall, CED of ILs plus successive laser-assisted PTT/PDT may be an alternative approach for treating brain tumor, which can retard glioma growth and prolong animal survival times from orthotopic brain tumor models.

Activated Platelet‐Targeted IR780 Immunoliposomes for Photothermal Thrombolysis

“…IR-L in PBS showed a strong and slightly shifted absorbance peak at 790 nm (Figure 2a). A similar shift in absorbance peak of liposomal IR780 has been reported in the literature [33,[35][36] and may be attributed to slight changes in the refractive index of the surrounding microenvironment. The absorbance decreased significantly when IR780 was freshly dispersed in PBS because of the instantaneous aggregation of lipophilic dye molecules in aqueous media.…”

“…The lipophilic IR780 dye was passively loaded to the liposome phospholipid bilayers at a dye/lipid molar ratio of 2 mol%. The selection of this dye/lipid molar ratio was based on previous reports [32][33][34] and our pilot studies (Figure S5, Supporting Information) toward minimal fluorescence self-quenching and optimal photothermal effects. IR-L in PBS showed a strong and slightly shifted absorbance peak at 790 nm (Figure 2a).…”

In vivo fluorescence imaging: success in preclinical imaging paves the way for clinical applications

“…The prepared IR780-encapsulated NPs showed higher hydrodynamic stability and photostability in aqueous medium compared to the free dye. Similar observations were reported when IR780 was encapsulated in different types of nanocarriers [ 91 ] such as transferrin NPs [ 92 ], lipid NPs [ 93 ], liposomes [ 94 ], and micelles [ 95 ]. Wu et al used an amphiphilic PEG-conjugated phospholipid (DSPE-PEG) to prepare hydrophilic micelles encapsulating the hydrophobic NIR-II fluorescent dye BPST.…”

Albumin-based nanoparticle for dual-modality imaging of the lymphatic system

“…IR-780 is a uorescent dye that has been studied more recently and will be the focus of our research. [34][35][36] Transverse tomography is non-invasive and facilitates rapid examination. On MRI, normal lymph nodes are usually less than 1 cm in size, with smooth and clear boundaries and uniform internal signal and density, and are generally oval or elongated.…”

“…IR-780 is a fluorescent dye that has been studied more recently and will be the focus of our research. 34–36…”