TY - JOUR
T1 - Nano-Assembly of Pamitoyl-Bioconjugated Coenzyme-A for Combinatorial Chemo-Biologics in Transcriptional Therapy
AU - Misra, Santosh K.
AU - Kampert, Taylor L.
AU - Pan, DIpanjan
N1 - Funding Information:
We acknowledge University of Illinois at Urbana−Champaign, National Institute of Health and Children’s Discovery Institute for financial assistance. We thank Dr. Tor Jensen for help with the FACS analysis. SAXS, TEM and zeta potential were carried out at Frederick Seitz Materials Research Laboratory Central research facilities, UIUC.
Funding Information:
We acknowledge University of Illinois at Urbana-Champaign, National Institute of Health and Children's Discovery Institute for financial assistance. We thank Dr. Tor Jensen for help with the FACS analysis. SAXS, TEM and zeta potential were carried out at Frederick Seitz Materials Research Laboratory Central research facilities, UIUC.
Publisher Copyright:
© 2018 American Chemical Society.
PY - 2018/4/18
Y1 - 2018/4/18
N2 - Pathogenesis, the biological mechanism that leads to the diseased state, of many cancers is driven by interruptions to the role of Myc oncoprotein, a regulator protein that codes for a transcription factor. One of the most significant biological interruptions to Myc protein is noted as its dimerization with Max protein, another important factor of family of transcription factors. Binding of this heterodimer to E-Boxes, enhancer boxes as DNA response element found in some eukaryotes that act as a protein-binding site and have been found to regulate gene expression, are interrupted to regulate cancer pathogenesis. The systemic effectiveness of potent small molecule inhibitors of Myc-Max dimerization has been limited by poor bioavailability, rapid metabolism, and inadequate target site penetration. The potential of gene therapy for targeting Myc can be fully realized by successful synthesis of a smart cargo. We developed a "nuclein" type nanoparticle "siNozyme" (45 ± 5 nm) from nanoassembly of pamitoyl-bioconjugated acetyl coenzyme-A for stable incorporation of chemotherapeutics and biologics to achieve remarkable growth inhibition of human melanoma. Results indicated that targeting transcriptional gene cMyc with siRNA with codelivery of a topoisomerase inhibitor, amonafide caused ∼90% growth inhibition and 95% protein inhibition.
AB - Pathogenesis, the biological mechanism that leads to the diseased state, of many cancers is driven by interruptions to the role of Myc oncoprotein, a regulator protein that codes for a transcription factor. One of the most significant biological interruptions to Myc protein is noted as its dimerization with Max protein, another important factor of family of transcription factors. Binding of this heterodimer to E-Boxes, enhancer boxes as DNA response element found in some eukaryotes that act as a protein-binding site and have been found to regulate gene expression, are interrupted to regulate cancer pathogenesis. The systemic effectiveness of potent small molecule inhibitors of Myc-Max dimerization has been limited by poor bioavailability, rapid metabolism, and inadequate target site penetration. The potential of gene therapy for targeting Myc can be fully realized by successful synthesis of a smart cargo. We developed a "nuclein" type nanoparticle "siNozyme" (45 ± 5 nm) from nanoassembly of pamitoyl-bioconjugated acetyl coenzyme-A for stable incorporation of chemotherapeutics and biologics to achieve remarkable growth inhibition of human melanoma. Results indicated that targeting transcriptional gene cMyc with siRNA with codelivery of a topoisomerase inhibitor, amonafide caused ∼90% growth inhibition and 95% protein inhibition.
UR - http://www.scopus.com/inward/record.url?scp=85045557723&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85045557723&partnerID=8YFLogxK
U2 - 10.1021/acs.bioconjchem.8b00117
DO - 10.1021/acs.bioconjchem.8b00117
M3 - Article
C2 - 29466855
AN - SCOPUS:85045557723
SN - 1043-1802
VL - 29
SP - 1419
EP - 1427
JO - Bioconjugate Chemistry
JF - Bioconjugate Chemistry
IS - 4
ER -
