



@article {3299,
	title = {Actively targeted cetuximab conjugated γ-poly(glutamic acid)-docetaxel nanomedicines for epidermal growth factor receptor over expressing colon cancer cells},
	journal = {Journal of Biomedical Nanotechnology},
	volume = {10},
	year = {2014},
	note = {Cited By (since 1996):1Export Date: 21 November 2014},
	month = {2014},
	pages = {1416 - 1428},
	abstract = {Receptor targeted therapy is advantageous in overcoming the toxicity burden of conventional cancer chemotherapeutics. Over expression of epidermal growth factor receptor (EGFR) on cancer cells and its role in metastasis, malignancy and drug resistance in many human cancers lead to its selection as a promising target for cancer treatment. The present work investigated the preparation and characterization of docetaxel (DTXL) loaded γ-poly (glutamic acid) (γ-PGA) nanoparticles (Nps) conjugated with EGFR antibody (Cetuximab, CET) targeted to colon cancer cells (HT-29), highly over expressing EGFR. The flow cytometric analysis revealed two fold increased cellular uptake of CET-DTXL-γ-PGA Nps by HT-29 (EGFR +ve) cells compared to that of IEC-6 (EGFR-ve) cells confirming the active targeting. Cytotoxicity assays (MTT and LDH) showed superior anti-proliferative activity of CET-DTXL-γ-PGA NPs over DTXL-γ-PGA Nps against HT-29 cells. The cell cycle analysis indicated that CET-DTXL-γ-PGA NPs induced cell death in enhanced percentage of HT-29 cells by undergoing cell cycle arrest in G2/M phase compared to that of DTXL-γ-PGA Nps. The mechanism of cancer cell death was analyzed via apoptotic and mitochondrial membrane potential assays and showed that targeted Nps treatment reduced the mitochondrial membrane potential thereby inducing enhanced HT-29 cell death (apoptosis and necrosis). The biodistribution of targeted and non-targeted Nps were analyzed in vivo in Swiss albino mice using NIR imaging. ICG-CET-DTXL-γ-PGA Nps (targeted) and ICG-DTXL-γ-PGA Nps (non-targeted) followed the similar biodistribution pattern in vivo, but with different elimination time. In short, CET-DTXL-γ-PGA nanoparticles enhance the tumor selective therapeutic efficacy for colon cancer. Copyright {\textcopyright} 2014 American Scientific Publishers All rights reserved.},
	keywords = {Cetuximab, colon cancer, Docetaxel, Epidermal growth factor receptor, Poly(γ-glutamic acid) nanoparticles, Targeted nanomedicines},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84899683740\&partnerID=40\&md5=39d65057952b3e192590262631867971},
	author = {Maya, S. and Sarmento, B. and Lakshmanan, V.-K. and Menon, D. and Jayakumar, R.}
}
@article {3300,
	title = {Chitosan cross-linked docetaxel loaded EGF receptor targeted nanoparticles for lung cancer cells},
	journal = {International Journal of Biological Macromolecules},
	volume = {69},
	year = {2014},
	note = {Cited By (since 1996):1Export Date: 21 November 2014},
	month = {2014},
	pages = {532 - 541},
	abstract = {Lung cancer, associated with the up-regulated epidermal growth factor receptor (EGFR) led to the development of EGFR targeted anticancer therapeutics. The biopolymeric nanoparticles form an outstanding system for the targeted delivery of therapeutic agents. The present work evaluated the in vitro effects of chitosan cross-linked γ-poly(glutamic acid) (γ-PGA) nanoparticles (Nps) loaded with docetaxel (DTXL) and decorated with Cetuximab (CET), targeted to EGFR over-expressing non-small-cell-lung-cancer (NSCLC) cells (A549). CET-DTXL-γ-PGA Nps was prepared by ionic gelation and CET conjugation via EDC/NHS chemistry. EGFR specificity of targeted Nps was confirmed by the higher uptake rates of EGFR +ve A549 cells compared to that of EGFR -ve cells (NIH3T3). The cytotoxicity of Nps quantified using cell based (MTT/LDH) and flowcytometry (Cell-cycle analysis, Annexin V/PI and JC-1) assays showed superior antiproliferative activity of CET-DTXL-γ-PGA Nps over DTXL-γ-PGA Nps. The A549 cells treated with CET-DTXL-γ-PGA NPs underwent a G2/M phase cell cycle arrest followed by reduction in mitochondrial membrane potential of A549 cells, inducing apoptosis and necrosis resulting in enhanced cancer cell death. CET-DTXL-γ-PGA Nps exhibited enhanced cellular internalization and therapeutic activity, by actively targeting EGFR on NSCLC cells and hence could be an effective alternative to non-specific, conventional chemotherapy by increasing its efficiency by many folds. {\textcopyright} 2014 Elsevier B.V.},
	keywords = {Cetuximab, chitosan, Epidermal growth factor receptor, Poly(γ-glutamic acid) nanoparticles, Targeted nanoparticles},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84903523289\&partnerID=40\&md5=728cbd3502e7922319f5f88fa8d6ec6d},
	author = {Maya, S. and Sarmento, B. and Lakshmanan, V.-K. and Menon, D. and Seabra, V. and Jayakumar, R.}
}
@article {3304,
	title = {Mad2 checkpoint gene silencing using epidermal growth factor receptor-targeted chitosan nanoparticles in non-small cell lung cancer model},
	journal = {Molecular Pharmaceutics},
	volume = {11},
	year = {2014},
	note = {Export Date: 21 November 2014},
	month = {2014},
	pages = {3515 - 3527},
	abstract = {RNA interference has emerged as a powerful strategy in cancer therapy because it allows silencing of specific genes associated with tumor progression and resistance. Mad2 is an essential mitotic checkpoint component required for accurate chromosome segregation during mitosis, and its complete abolition leads to cell death. We have developed an epidermal growth factor receptor (EGFR)-targeted chitosan system for silencing the Mad2 gene as a strategy to efficiently induce cell death in EGFR overexpressing human A549 non-small cell lung cancer cells. Control and EGFR-targeted chitosan nanoparticles loaded with small interfering RNAs (siRNAs) against Mad2 were formulated and characterized for size, charge, morphology, and encapsulation efficiency. Qualitative and quantitative intracellular uptake studies by confocal imaging and flow cytometry, respectively, showed time-dependent enhanced and selective intracellular internalization of EGFR-targeted nanoparticles compared to nontargeted system. Targeted nanoparticles showed nearly complete depletion of Mad2 expression in A549 cells contrasting with the partial depletion in the nontargeted system. Accordingly, Mad2-silencing-induced apoptotic cell death was confirmed by cytotoxicity assay and flow cytometry. Our results demonstrate that EGFR-targeted chitosan loaded with Mad2 siRNAs is a potent delivery system for selective killing of cancer cells.},
	keywords = {chitosan nanoparticles, Epidermal growth factor receptor, Mad2 gene, non-small cell lung cancer, RNA interference, tumor targeting},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84908009342\&partnerID=40\&md5=bc0130ca0bcdb576b7de6801c3517e93},
	author = {Nascimento, A.V. and Singh, A. and Bousbaa, H. and Ferreira, D. and Sarmento, B. and Amiji, M.M.}
}
