科研之友
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摘要
Drug delivery systems based on nanoparticles (nano-DDS) have aroused attentions for the treatment of glioblastoma (GBM), the most malignant brain cancer with a dismal prognosis. However, there are still numerous unmet challenges for traditional nano-DDS, such as the poor nanoparticle penetration, short retention in the GBM parenchyma and low glioma targeting ability. Herein, we used Pep-1 and CREKA peptides to construct a novel multifunctional GBM targeting nano-DDS (PC-NP). Pep-1 was used to overcome the blood-brain tumor barrier (BBTB) and home to glioma cells via interleukin-13 receptor-alpha 2-mediated endocytosis, and CREKA was used to bind to fibrin-fibronectin complexes abundantly expressed in tumor microenvironment for enhanced retention in the GBM. Biological studies showed that the cellular uptake of PC-NP by U87MG cells was significantly enhanced compared with the non-targeting NP. Furthermore, CREKA modification increased the binding capacity of PC-NP to fibrin-fibronectin complexes as confirmed by the competition experiment. In accordance with the increased cellular uptake, PC-NP remarkably increased the cytotoxicity of its payload paclitaxel (PTX) against U87MG cells with an IC50 of 0.176 mu g/mL. In vivo fluorescence imaging and antiglioma efficacy evaluation further confirmed that PC-NP accumulated effectively and penetrated deeply into GBM tissue. PC-NP-PTX exhibited a median survival time as long as 61 days in intracranial GBM-bearing mice. In conclusion, our findings indicated PC-NP as a promising nano-DDS for GBM targeting delivery of anticancer drugs.
