Anti-SSTR2 peptide based targeted delivery of potent PLGA encapsulated 3,3’-diindolylmethane nanoparticles through blood brain barrier prevents glioma progression
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Arijit Bhowmik1, Sayak Chakravarti1,*, Aparajita Ghosh2,*, Rajni Shaw1,*, Suman Bhandary2, Satyaranjan Bhattacharyya3, Parimal C. Sen2 and Mrinal K. Ghosh1
1Signal Transduction in Cancer and Stem Cells Laboratory, Translational Research Unit of Excellence (TRUE), Division of Cancer Biology and Inflammatory Disorder, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology (CSIR-IICB), Kolkata 700091, India
2Division of Molecular Medicine, Bose Institute, Centenary Campus, Kolkata 700054, India
3Division of Surface Physics, Saha Institute of Nuclear Physics, Kolkata 700064, India
*These authors have contributed equally to this work
Mrinal K. Ghosh, email: [email protected]
Keywords: glioma, blood brain barrier, 3,3’-diindolylmethane encapsulated nanoparticle, somatostatin receptor 2 peptide, epidermal growth factor receptor
Received: November 22, 2016 Accepted: May 22, 2017 Published: June 27, 2017
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.
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