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

被引:34
作者
Bhowmik, Arijit [1 ]
Chakravarti, Sayak [1 ]
Ghosh, Aparajita [2 ]
Shaw, Rajni [1 ]
Bhandary, Suman [2 ]
Bhattacharyya, Satyaranjan [3 ]
Sen, Parimal C. [2 ]
Ghosh, Mrinal K. [1 ]
机构
[1] CSIR IICB, Div Canc Biol & Inflammatory Disorder, TRUE, Signal Transduct Canc & Stem Cells Lab, Kolkata 700091, India
[2] Bose Inst, Div Mol Med, Centenary Campus, Kolkata 700054, India
[3] Saha Inst Nucl Phys, Div Surface Phys, Kolkata 700064, India
关键词
glioma; blood brain barrier; 3,3 '-diindolylmethane encapsulated nanoparticle; somatostatin receptor 2 peptide; epidermal growth factor receptor; BOX PROTEIN P68; IN-VITRO; BRASSICA VEGETABLES; CANCER-RISK; MARKERS; VCAM-1; GROWTH; TUMORS; ICAM-1; STAT3;
D O I
10.18632/oncotarget.18689
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:65339 / 65358
页数:20
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