Publication Type:

Journal Article

Source:

Journal of Biomedical Nanotechnology, American Scientific Publishers, Volume 10, Number 8, p.1401-1415 (2014)

URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-84899694250&partnerID=40&md5=52c217cf3472a3f8d797834278a21dd9

Keywords:

albumin, Albumins, alcohol, animal experiment, animal model, animal tissue, Animals, Antineoplastic Agents, apoptosis, article, biocompatibility, cancer cell, cancer cell culture, Cell death, Cell Line, cell migration, cell migration assay, Cell Movement, Cell Survival, controlled study, Copolymers, Core-shell, cytotoxicity, Dasatinib, Diseases, down regulation, Drug Carriers, electrospray, Electrospray techniques, Enzymes, fluorescence activated cell sorting, glioma cell, Glioma. mTHPP, human, human cell, human cell culture, Humans, immunoblotting, in vitro study, in vivo study, Intravenous administration, Lactic acid, laser, male, Medical nanotechnology, nanomedicine, nanoshell, nonhuman, Oxygen, particle size, pathology, Photodynamic therapy, Photophysical properties, photosensitization, Photosensitizers, photosensitizing agent, Photosensitizing Agents, phototherapy, Physiological condition, Poly(lactic-co-glycolic acid), polyglactin, polyglycolic acid, polymer, Polymers, porphyrin derivative, Porphyrins, Proteins, Pyrimidines, rat, Rats, reactive oxygen metabolite, scanning electron microscopy, Shells (structures), signal transduction, singlet oxygen, Stress, Thiazoles, toxicity, transmission electron microscopy, Tumor, Tumors, Wistar

Abstract:

Migratory capacity of cancer plays a critical role in the process of metastasis. Aberrant focal adhesions activated by the phosphorylation of Src kinase enables cancer cells to anchor on its micro-environment and migrate towards biochemically favorable niche, causing metastasis. Effective blocking of the migratory capacity of cancer cells by inhibiting protein kinases and subsequent application of cytotoxic stress may provide better therapeutic outcome. Here, we report a novel core-shell nanomedicine that inhibits cancer migration by nano-shell and impart reactive oxygen stress by laser assisted photosensitization of nano-core. For this, we have optimized a polymer-protein nanoconstruct where a photosensitizer (5,10,15, 20-tetrakis(meso-hydroxyphenyl) porphyrin (mTHPP) is loaded into poly(lactic-co-glycolic acid) (PLGA) nano-core and Src kinase inhibitor (dasatinib) is loaded into albumin nano-shell. The polymer-core was prepared by electrospray technique and albumin-shell was formed by alcohol coacervation. Transmission electron microscopy studies revealed the formation of ∼80 nm sized nano-core decorated with ∼10 nm size nano-shell. Successful incorporation of monomeric mTHPP in nano-core resulted improved photo-physical properties and singlet oxygen release under physiological conditions compared to free-mTHPP. Core-shell nanomedicine also showed dose and time dependent cellular uptake in U87MG glioma cells. Dasatinib released from nano-shell caused down regulation of phospho-Src leading to significant impairment of cancer migration and subsequent laser assisted photosensitization of nano-core resulted in the release of reactive oxygen stress leading to apoptosis of spatially confined cancer cells. In vivo studies on Wistar rats indicated the absence of any significant toxicity caused by the intravenous administration of nanomedicine. These results clearly show the advantage of core-shell nanomedicine mediated combinatorial approach for inhibiting important cancer signalling pathways togother with imparting cytotoxic stress. Copyright © 2014 American Scientific Publishers All rights reserved.

Notes:

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Cite this Research Publication

, “A polymer-protein core-shell nanomedicine for inhibiting cancer migration followed by photo-triggered killing”, Journal of Biomedical Nanotechnology, vol. 10, pp. 1401-1415, 2014.