Comparison of three synthetic transferrin mimetic small peptides to promote the blood–brain barrier penetration of vincristine liposomes for improved glioma targeted therapy

The existence of the blood–brain barrier (BBB) makes the clinical chemotherapy of glioma a formidable challenge, because it hinders the passage of different chemotherapeutics into the brain and reduces the overall therapeutic efficiency. Therefore, it is necessary to design a drug delivery system in way that would favor the transportation of anti-cancer agents across the BBB and increase their selective accumulation within the tumor cells without affecting the normal tissues. Transferrin receptor (TfR) that shows an elevated level of expression on the BBB and glioma cells emerges as a promising tool for brain targeted delivery and glioma therapy. However, only a limited number of studies have comparatively evaluated the functionally of TfR targeting ligands. Herein, a series of liposomal formulations modified with the most well-known TfR targeting peptides including T12 (also known as THR), B6, and T7 was developed and their brain targeting capability and selective glioma accumulation was comparatively evaluated in vitro and in vivo. Among all TfR targeting or non-targeting groups, T7-modified liposomes (T7-LS) showed the highest BBB penetration capacity and brain distribution and displayed an enhanced accumulation in glioma cells. When loaded with vincristine (VCR), as a model chemotherapeutic, T7-LS/VCR could achieve the best anti-glioma outcome by means of targeted cytotoxicity and apoptosis in vitro. The obtained results suggested T7-LS as a potential platform for effective brain targeted delivery and glioma therapy in clinic.