PMID- 25198921 OWN - NLM STAT- MEDLINE DCOM- 20160310 LR - 20231213 IS - 1520-5126 (Electronic) IS - 0002-7863 (Linking) VI - 136 IP - 42 DP - 2014 Oct 22 TI - A gold nanoparticle pentapeptide: gene fusion to induce therapeutic gene expression in mesenchymal stem cells. PG - 14763-71 LID - 10.1021/ja505190q [doi] AB - Mesenchymal stem cells (MSC) have been identified as having great potential as autologous cell therapeutics to treat traumatic brain injury and spinal injury as well as neuronal and cardiac ischemic events. All future clinical applications of MSC cell therapies must allow the MSC to be harvested, transfected, and induced to express a desired protein or selection of proteins to have medical benefit. For the full potential of MSC cell therapy to be realized, it is desirable to systematically alter the protein expression of therapeutically beneficial biomolecules in harvested MSC cells with high fidelity in a single transfection event. We have developed a delivery platform on the basis of the use of a solid gold nanoparticle that has been surface modified to produce a fusion containing a zwitterionic, pentapeptide designed from Bax inhibiting peptide (Ku70) to enhance cellular uptake and a linearized expression vector to induce enhanced expression of brain-derived neurotrophic factor (BDNF) in rat-derived MSCs. Ku70 is observed to effect >80% transfection following a single treatment of femur bone marrow isolated rat MSCs with efficiencies for the delivery of a 6.6 kbp gene on either a Au nanoparticle (NP) or CdSe/ZnS quantum dot (QD). Gene expression is observed within 4 d by optical measurements, and secretion is observed within 10 d by Western Blot analysis. The combination of being able to selectively engineer the NP, to colocalize biological agents, and to enhance the stability of those agents has provided the strong impetus to utilize this novel class of materials to engineer primary MSCs. FAU - Muroski, Megan E AU - Muroski ME AD - Department of Chemistry and Biochemistry, 95 Chieftan Way, Florida State University , Tallahassee, Florida 32306-4390, United States. FAU - Morgan, Thomas J Jr AU - Morgan TJ Jr FAU - Levenson, Cathy W AU - Levenson CW FAU - Strouse, Geoffrey F AU - Strouse GF LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20141007 PL - United States TA - J Am Chem Soc JT - Journal of the American Chemical Society JID - 7503056 RN - 0 (Antigens, Nuclear) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (DNA-Binding Proteins) RN - 0 (Drug Carriers) RN - 0 (Luminescent Proteins) RN - 0 (Oligopeptides) RN - 0 (Peptide Fragments) RN - 7440-57-5 (Gold) RN - EC 3.6.4.12 (Xrcc6 protein, rat) RN - EC 4.2.99.- (Ku Autoantigen) SB - IM MH - Animals MH - Antigens, Nuclear/chemistry MH - Brain-Derived Neurotrophic Factor/genetics MH - Cell- and Tissue-Based Therapy MH - DNA-Binding Proteins/chemistry MH - Drug Carriers/*chemistry MH - Gene Expression MH - *Gene Fusion MH - Gold/*chemistry MH - Ku Autoantigen MH - Luminescent Proteins/genetics MH - Mesenchymal Stem Cells/*metabolism MH - *Metal Nanoparticles MH - Oligopeptides/*chemistry MH - Peptide Fragments/chemistry MH - Quantum Dots/chemistry MH - Rats MH - Transfection/*methods MH - Red Fluorescent Protein EDAT- 2014/09/10 06:00 MHDA- 2016/03/11 06:00 CRDT- 2014/09/09 06:00 PHST- 2014/09/09 06:00 [entrez] PHST- 2014/09/10 06:00 [pubmed] PHST- 2016/03/11 06:00 [medline] AID - 10.1021/ja505190q [doi] PST - ppublish SO - J Am Chem Soc. 2014 Oct 22;136(42):14763-71. doi: 10.1021/ja505190q. Epub 2014 Oct 7.