Targeted delivery strategy of indocyanine green-mitoxantrone loaded liposomes co-modified with BTP-7 and BR2 for the treatment of glioma

Abstract

Objective: This study aims to develop a dual-ligand-modified targeted drug delivery system by integrating photosensitizers and chemotherapeutic drugs to enhance anti-glioma effects. The system is designed to overcome the blood-brain barrier (BBB) that hinders effective drug delivery, increase drug accumulation in glioma cells, and thereby enhance therapeutic efficacy.

Methods: Liposomes were prepared using the film dispersion-ammonium sulfate gradient technique, co-loading the photosensitizer indocyanine green (ICG) and the chemotherapeutic drug mitoxantrone (MTO). The conjugation of BTP-7 and BR2 to the liposome surface was achieved using an organic phase reaction method. The stability, dispersibility, particle size, and potential of the modified liposomes were tested. Their ability to penetrate the BBB and accumulate in glioma was evaluated in BBB models and cellular uptake studies. Additionally, the anti-tumor activity of this combination approach was assessed.

Results: The resulting liposomes demonstrated significant stability and dispersibility, with an average particle size of 142.3 ± 1.8 nm and a potential of -17.6 mV. BBB model and cellular uptake studies indicated that BTP-7/BR2-ICG/MTO-LP could not only penetrate the BBB but also accumulate in glioma, leading to glioma cell necrosis. The anti-tumor activity evaluation showed that this combination approach exhibited a strong tumor-suppressing effect.

Conclusion: The dual-ligand-modified liposomes developed in this study can penetrate the blood-brain barrier and achieve targeted drug delivery in glioma therapy. The combination of BTP-7 and BR2 not only enhances the carrier's penetration ability but also increases intracellular drug accumulation, thereby improving therapeutic efficacy. This novel therapeutic approach, which combines chemotherapy and photothermal response via dual-ligand-modified liposomes delivered to the tumor site, demonstrates the potential to reduce drug-related side effects and improve treatment outcomes.

Keywords: BR2 penetrating peptide; BTP-7; GMB; Nano-delivery system; PDT; liposome.