title: Intra-tumoral delivery of functional ID4 protein via PCL/maltodextrin nano-particle inhibits prostate cancer growth.
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.
authors.affiliation: College of Pharmacy, Mercer University, Atlanta, GA, USA.
authors.forename: Maxwell
authors.initials: M
authors.lastname: Korang-Yeboah
authors.affiliation: Center for Cancer Research and Therapeutic Development, Clark Atlanta University, Atlanta, GA, USA.
authors.forename: Divya
authors.initials: D
authors.lastname: Patel
authors.affiliation: Center for Cancer Research and Therapeutic Development, Clark Atlanta University, Atlanta, GA, USA.
authors.forename: Derrick
authors.initials: D
authors.lastname: Morton
authors.affiliation: Center for Cancer Research and Therapeutic Development, Clark Atlanta University, Atlanta, GA, USA.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Sharma
authors.affiliation: College of Pharmacy, Mercer University, Atlanta, GA, USA.
authors.forename: Yamini
authors.initials: Y
authors.lastname: Gorantla
authors.affiliation: Center for Cancer Research and Therapeutic Development, Clark Atlanta University, Atlanta, GA, USA.
authors.forename: Jugal
authors.initials: J
authors.lastname: Joshi
authors.affiliation: Center for Cancer Research and Therapeutic Development, Clark Atlanta University, Atlanta, GA, USA.
authors.forename: Perri
authors.initials: P
authors.lastname: Nagappan
authors.affiliation: College of Pharmacy, Mercer University, Atlanta, GA, USA.
authors.forename: Ravi
authors.initials: R
authors.lastname: Pallaniappan
authors.affiliation: Center for Cancer Research and Therapeutic Development, Clark Atlanta University, Atlanta, GA, USA.
authors.forename: Jaideep
authors.initials: J
authors.lastname: Chaudhary
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D000077143:Docetaxel; D004337:Drug Carriers / Q000737:chemistry; D006801:Humans; D051796:Inhibitor of Differentiation Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008297:Male; D016513:Mice, SCID; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D011091:Polyesters / Q000737:chemistry; D011134:Polysaccharides / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D043823:Taxoids / Q000494:pharmacology; D047368:Tumor Burden / Q000187:drug effects / Q000235:genetics; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; C490128:ID4 protein, human; D051796:Inhibitor of Differentiation Proteins; D011091:Polyesters; D011134:Polysaccharides; D043823:Taxoids; D000077143:Docetaxel; C016240:polycaprolactone; C008315:maltodextrin
keywords: ID4; nano-carrier; prostate cancer; protein delivery; tumor suppressor