Intra-tumoral delivery of functional ID4 protein via PCL/maltodextrin nano-particle inhibits prostate cancer growth

2016 
// Maxwell Korang-Yeboah 1, * , Divya Patel 2, * , Derrick Morton 2 , Pankaj Sharma 2 , Yamini Gorantla 1 , Jugal Joshi 2 , Perri Nagappan 2 , Ravi Pallaniappan 1 , Jaideep Chaudhary 2 1 College of Pharmacy, Mercer University, Atlanta, GA, USA 2 Center for Cancer Research and Therapeutic Development, Clark Atlanta University, Atlanta, GA, USA * These authors have contributed equally to this work Correspondence to: Jaideep Chaudhary, email: jchaudhary@cau.edu Keywords: ID4, prostate cancer, tumor suppressor, nano-carrier, protein delivery Received: March 11, 2016      Accepted: June 30, 2016      Published: July 30, 2016 ABSTRACT ID4, a helix loop helix transcriptional regulator has emerged as a tumor suppressor in prostate cancer. Epigenetic silencing of ID4 promotes prostate cancer whereas ectopic expression in prostate cancer cell lines blocks cancer phenotype. To directly investigate the anti-tumor property, full length human recombinant ID4 encapsulated in biodegradable Polycaprolactone/Maltodextrin (PCL-MD) nano-carrier was delivered to LNCaP cells in which the native ID4 was stably silenced (LNCaP(-)ID4). The cellular uptake of ID4 resulted in increased apoptosis, decreased proliferation and colony formation. Intratumoral delivery of PCL-MD ID4 into growing LNCaP(-)ID4 tumors in SCID mice significantly reduced the tumor volume compared to the tumors treated with chemotherapeutic Docetaxel. The study supports the feasibility of using nano-carrier encapsulated ID4 protein as a therapeutic. Mechanistically, ID4 may assimilate multiple regulatory pathways for example epigenetic re-programming, integration of multiple AR co-regulators or signaling pathways resulting in tumor suppressor activity of ID4.
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