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Zhao YZ, Chen LJ, Lin Q, Cai J, Yu WZ, Zhao YP, Xu CY, Mao KL, Tian FR, Li WF, Wong HL, Lu CT
Using FUS induced BBB/BTB-opening technique combined with Doxorubicin liposomes to improve glioma-targeted inhibition
Oncotarget (2015) In process.
PURPOSE: Blood-brain barrier and blood-tumor barrier (BBB/BTB) are the main limitations for chemotherapeutics in glioma therapy. Focused ultrasound (FUS) combined novel Doxorubicin-loaded liposomes (LIP-DOX) was applied to open the BBB/BTB and improve the efficiency of glioma-targeted chemotherapy. EXPERIMENTAL DESIGNS: Particle size, Zeta potential and drug encapsulation efficiency were evaluated. C6 glioma model rats were established to evaluate the BBB/BTB disruption and the glioma inhibition in vivo. With Evans Blue (EB) as the model, the permeability of BBB/BTB was evaluated. The glioma inhibition of FUS+LIP-DOX was investigated by magnetic resonance images (MRI) and confocal laser microscope. The activities of beta1-intergrin and claudin-5 proteins in response to FUS-mediated BBB/BTB opening were explored. RESULTS: LIP-DOX has suitable nanoscale size and good polydispersity index. From EB extravasation experiment, FUS increased the BBB/BTB penetration and accumulation of EB in the glioma. LIP-DOX combined with FUS could efficiently enhance DOX penetrate into the model rat brains, realizing strong glioma inhibition in vivo. Among DOX-administrated groups, FUS+LIP-DOX group showed the beat inhibition on glioma. FUS+LIP-DOX group reduced the tumor progression ratio from 1.18 to -0.20, extending the median survival from 23d to 57.5d. beta1-intergrin and claudin-5 were significantly decreased after FUS treatment, which explained the molecular mechanisms of BBB-opening by FUS. CONCLUSIONS: Glioma-targeted inhibition can be realized by using FUS induced BBB/BTB-opening technique combined with LIP-DOX. This combined technology will be developed as a potential strategy for glioma-targeted therapy.
Publication Date: 2015-09-02.
Last updated on Saturday, August 22, 2020