Tumor cellular membrane camouflaged liposomes as the non-invasive vehicle of gene: the specific targeting toward homologous glioma and the traversing blood brain barrier
Gene therapy of malignant gliomas has shown a limited success to date due in part to inability of conventional gene vectors to achieve widespread and specific gene transfer throughout highly disseminated tumor zone within the brain. Herein, cationic micelles assembled by vitamin E succinate-grafted ε-polylysine (VES-g-PL) polymer were firstly exploited to condense TRAIL plasmid (pDNA). Thereafter, the condensed pDNA were further encapsulated into liposome camouflaged with tumor cellular membrane. The condensed pDNA were successfully encapsulated into the inner aqueous compartment of liposome instead of its surface, which were proved by TEM morphology and the decreased cytotoxicity toward HUVEC or PC-12 cells. Moreover, glioma cells membrane (CM) was easily inlaid into the lipid layer of pDNA-loaded liposome to form T@VP-MCL, as testified by TEM, AFM and SDS-PAGE analysis. T@VP-MCL exhibited a good stability of particle size under strong ion strength and effectively protected pDNA from DNase I degradation. Owing to the CM-associated proteins, T@VP-MCL targeted not only specifically ICAM-1 overexpressed on RBMECs of glioma but also the homogenous glioma cells. Moreover, in vivo imaging showed that T@VP-MCL was effectively homed to the orthotropic glioma of rats after intravenous administration, resulting in the effective tumor growth inhibition and prolonging the life of rats. The mechanism of traversing BBB for T@VP-MCL was highly associated with down-regulation of tight junction-associated proteins, ZO-1 and Claudin-5. Conclusively, the designed T@VP-MCL may be a potential carrier for therapeutic gene.