Delivering siRNA and Chemotherapeutic Molecules Across BBB and BTB for Intracranial Glioblastoma Therapy.
For aggressive brain glioblastoma, the therapy is significantly impaired by blood-brain barrier (BBB) and blood-tumor barrier (BTB). Choosing more than one target from the pool of tumor-stroma interactions is profoundly beneficial to therapeutic approaches. Thus, a multifunctional liposomal system based on anchoring two receptor-specific and penetrable peptides was designed for the combination delivery of BBB-impermeable siRNA and chemotherapeutic docetaxel to brain glioblastoma. Both macroscopic and microscopic specific distributions and targeting effect of the liposomes in the intracranial glioblastoma were confirmed. Superiority in therapeutic efficacies of the siRNA and DTX combination delivery system was revealed from encouraged VEGF gene silencing, tumor cell apoptosis, prolonged survival time, subdued glioblastoma cells in intracranial glioblastoma, and negligible system toxicities after systemic application. Furthermore, the liposomes made better modulation of glioblastoma microenvironment such as the down-regulation of CD31-positive tumor vessels and HIF-1α expression. The transport mechanism of the liposomes delivering the cargos across BBB via receptor-mediated transcytosis without destroying the integrity of BBB has been evaluated from in vitro and in vivo. Therefore, the dual peptides-modified liposomal system provides a safe and noninvasive approach for the delivery of siRNA and chemotherapeutic molecules across the BBB and BTB to target therapy of brain glioblastoma.
['Yang|Zhen-Zhen|ZZ|', 'Gao|Wei|W|', 'Liu|Yu-Jie|YJ|', 'Pang|Ning|N|', 'Qi|Xian-Rong|XR|0000-0002-8264-0794']
D000818:Animals D000970:Antineoplastic Agents D017209:Apoptosis D001812:Blood-Brain Barrier D001932:Brain Neoplasms D045744:Cell Line, Tumor D000077143:Docetaxel D015536:Down-Regulation D020868:Gene Silencing D005909:Glioblastoma D006801:Humans D051795:Hypoxia-Inducible Factor 1, alpha Subunit D008081:Liposomes D051379:Mice D010455:Peptides D034741:RNA, Small Interfering D043823:Taxoids D059016:Tumor Microenvironment D042461:Vascular Endothelial Growth Factor A
glioblastoma receptor-mediated transcytosis biodistribution blood−brain barrier blood−tumor barrier real-time bioluminescence imaging tight junction