Anti-SSTR2 peptide based targeted delivery of potent PLGA encapsulated 3,3'-diindolylmethane nanoparticles through blood brain barrier prevents glioma progression

Oncotarget. 2017 Jun 27;8(39):65339-65358. doi: 10.18632/oncotarget.18689. eCollection 2017 Sep 12.

Abstract

Current therapy for Glioblastoma is insufficient because of the presence of blood brain barrier. It limits the transport of essential drugs to the tumor sites. To overcome this limitation we strategized the delivery of an anticancer compound 3,3'-diindolylmethane by encapsulation in poly (lactic-co-glycolic acid) nanoparticles. These nanoparticles were tagged with a novel peptide against somatostatin receptor 2 (SSTR2), a potential target in glioma. The nanoformulation (27-87nm) had loading and encapsulation efficiency of 7.2% and 70% respectively. It was successfully internalized inside the glioma cells resulting in apoptosis. Furthermore, an in vivo bio-distribution study revealed the selective accumulation of the nanoformulation into rat brain tumor sites by crossing the blood brain barrier. This resulted in abrogation of epidermal growth factor receptor pathway activation in glioma cells. Our novel nanopreparation therefore shows great promise to serve as a template for targeted delivery of other therapeutics in treating GBM.

Keywords: 3,3’-diindolylmethane encapsulated nanoparticle; blood brain barrier; epidermal growth factor receptor; glioma; somatostatin receptor 2 peptide.