Intra-tumoral delivery of functional ID4 protein via PCL/maltodextrin nano-particle inhibits prostate cancer growth
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Maxwell Korang-Yeboah1,*, Divya Patel2,*, Derrick Morton2, Pankaj Sharma2, Yamini Gorantla1, Jugal Joshi2, Perri Nagappan2, Ravi Pallaniappan1, Jaideep Chaudhary2
1College of Pharmacy, Mercer University, Atlanta, GA, USA
2Center for Cancer Research and Therapeutic Development, Clark Atlanta University, Atlanta, GA, USA
*These authors have contributed equally to this work
Jaideep Chaudhary, email: [email protected]
Keywords: ID4, prostate cancer, tumor suppressor, nano-carrier, protein delivery
Received: March 11, 2016 Accepted: June 30, 2016 Published: July 30, 2016
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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