Publication Type:

Journal Article

Source:

Nanomedicine: Nanotechnology, Biology, and Medicine, Volume 9, Number 8, p.1317-1327 (2013)

URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-84886444894&partnerID=40&md5=b92e806a40ee480e02f10e5c4707a1e8

Keywords:

Acute, acute granulocytic leukemia, acute granulocytic leukemia cell, albumin, Antibiotics, Antineoplastic Agents, apoptosis, article, assay, Blood, blood cell, cancer cell, Cancer kinome, CD33 antigen, CD34 antigen, CD38 antigen, Cell Line, Cell membranes, cell receptor, controlled study, Core-shell, Core-shell nanomedicine, cytarabine, cytotoxicity, daunorubicin, Design, Diseases, Drug Delivery Systems, electron microscopy, Enzymes, everolimus, flow cytometry, Functional polymers, human, human cell, Humans, immunoblotting, Kinase inhibitors, lethality, Leukemia, leukemia cell, mammalian target of rapamycin, Medical nanotechnology, mitogen activated protein kinase, Mitogen-Activated Protein Kinases, Models, Molecular, Monoclonal antibodies, monoclonal antibody, Myeloid, nanomaterial, nanomedicine, Niacinamide, Phenylurea Compounds, polyglactin, Polyglactin 910, polymer, Protein Kinase Inhibitors, Proteins, Shells (structures), Sialic Acid Binding Ig-like Lectin 3, Sirolimus, sorafenib, STAT5 protein, STAT5 Transcription Factor, Targeting, TOR Serine-Threonine Kinases, Tumor

Abstract:

Simultaneous inhibition of deregulated cancer kinome using rationally designed nanomedicine is an advanced therapeutic approach. Herein, we have developed a polymer-protein core-shell nanomedicine to inhibit critically aberrant pro-survival kinases (mTOR, MAPK and STAT5) in primitive (CD34+/CD38-) Acute Myeloid Leukemia (AML) cells. The nanomedicine consists of poly-lactide-co-glycolide core ( 250nm) loaded with mTOR inhibitor, everolimus, and albumin shell ( 25nm thick) loaded with MAPK/STAT5 inhibitor, sorafenib and the whole construct was surface conjugated with monoclonal antibody against CD33 receptor overexpressed in AML. Electron microscopy confirmed formation of core-shell nanostructure ( 290nm) and flow cytometry and confocal studies showed enhanced cellular uptake of targeted nanomedicine. Simultaneous inhibition of critical kinases causing synergistic lethality against leukemic cells, without affecting healthy blood cells, was demonstrated using immunoblotting, cytotoxicity and apoptosis assays. This cell receptor plus multi-kinase targeted core-shell nanomedicine was found better specific and tolerable compared to current clinical regime of cytarabine and daunorubicin. From the Clinical Editor: These authors demonstrate simultaneous inhibition of critical kinases causing synergistic lethality against leukemic cells, without affecting healthy blood cells by using rationally designed polymer-protein core-shell nanomedicine, provoding an advanced method to eliminate cancer cells, with the hope of future therapeutic use. © 2013 Elsevier Inc.

Notes:

cited By 3

Cite this Research Publication

, “Simultaneous inhibition of aberrant cancer kinome using rationally designed polymer-protein core-shell nanomedicine”, Nanomedicine: Nanotechnology, Biology, and Medicine, vol. 9, pp. 1317-1327, 2013.