Back to Journals » International Journal of Nanomedicine » Volume 10 » Issue 1

Tumor-targeted and pH-controlled delivery of doxorubicin using gold nanorods for lung cancer therapy

Authors Amreddy N, Muralidharan R, Babu A, Mehta M, Johnson E, Zhao Y, Munshi A, Ramesh R

Received 28 July 2015

Accepted for publication 19 September 2015

Published 29 October 2015 Volume 2015:10(1) Pages 6773—6788


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Govarthanan Muthusamy

Peer reviewer comments 3

Editor who approved publication: Dr Thomas J Webster

Narsireddy Amreddy,1,2 Ranganayaki Muralidharan,1,2 Anish Babu,1,2 Meghna Mehta,2,3 Elyse V Johnson,4 Yan D Zhao,2,5 Anupama Munshi,2,3 Rajagopal Ramesh1,2,6

1Department of Pathology, 2Stephenson Cancer Center, 3Department of Radiation Oncology University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; 4CytoViva Inc., Auburn, AL, USA; 5Department of Biostatistics and Epidemiology, 6Graduate Program in Biomedical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

Background: In lung cancer, the efficacy of conventional chemotherapy is limited due to poor drug accumulation in tumors and nonspecific cytotoxicity. Resolving these issues will increase therapeutic efficacy.
Methods: GNR-Dox-Tf-NPs (gold nanorod-doxorubicin-transferrin-nanoparticles) were prepared by different chemical approaches. The efficacy of these nanoparticles was carried out by cell viability in lung cancer and primary coronary artery smooth muscle cells. The receptor-mediated endocytosis studies were done with human transferrin and desferrioxamine preincubation. The GNR-Dox-Tf nanoparticles induced apoptosis, and DNA damage studies were done by Western blot, H2AX foci, and comet assay.
Results: We developed and tested a gold nanorod-based multifunctional nanoparticle system (GNR-Dox-Tf-NP) that carries Dox conjugated to a pH-sensitive linker and is targeted to the transferrin receptor overexpressed in human lung cancer (A549, HCC827) cells. GNR-Dox-Tf-NP underwent physicochemical characterization, specificity assays, tumor uptake studies, and hyperspectral imaging. Biological studies demonstrated that transferrin receptor-mediated uptake of the GNR-Dox-Tf-NP by A549 and HCC827 cells produced increased DNA damage, apoptosis, and cell killing compared with nontargeted GNR-Dox-NP. GNR-Dox-Tf-NP-mediated cytotoxicity was greater (48% A549, 46% HCC827) than GNR-Dox-NP-mediated cytotoxicity (36% A549, 39% HCC827). Further, GNR-Dox-Tf-NP markedly reduced cytotoxicity in normal human coronary artery smooth muscle cells compared with free Dox.
Conclusion: Thus, GNR-Dox-Tf nanoparticles can selectively target and deliver Dox to lung tumor cells and alleviate free Dox-mediated toxicity to normal cells.

Keywords: doxorubicin, gold, lung cancer, nanoparticles, transferrin, tumor targeting

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]


Other articles by this author:

Drug resistance in lung cancer

Manish Shanker, David Willcutts, Jack A Roth, et al

Lung Cancer: Targets and Therapy 2010, 1:23-36

Published Date: 13 May 2010

Readers of this article also read:

Photosensitizer and peptide-conjugated PAMAM dendrimer for targeted in vivo photodynamic therapy

Narsireddy A, Vijayashree K, Adimoolam MG, Manorama SV, Rao NM

International Journal of Nanomedicine 2015, 10:6865-6878

Published Date: 3 November 2015

Long-term effects of gastrectomy in patients with spirometry-defined COPD and patients at risk of COPD: a case-control study

Saito H, Nomura K, Abe S, Motegi T, Ishii T, Hattori K, Kusunoki Y, Gemma A, Kida K

International Journal of Chronic Obstructive Pulmonary Disease 2015, 10:2311-2318

Published Date: 29 October 2015

Molecular targets in arthritis and recent trends in nanotherapy

Roy K, Kanwar RK, Kanwar JR

International Journal of Nanomedicine 2015, 10:5407-5420

Published Date: 26 August 2015

Targeted multidrug-resistance reversal in tumor based on PEG-PLL-PLGA polymer nano drug delivery system

Guo L, Zhang H, Wang F, Liu P, Wang Y, Xia G, Liu R, Li X, Yin H, Jiang H, Chen B

International Journal of Nanomedicine 2015, 10:4535-4547

Published Date: 16 July 2015

Patient preference and ease of use for different coagulation factor VIII reconstitution device scenarios: a cross-sectional survey in five European countries

Cimino E, Linari S, Malerba M, Halimeh S, Biondo F, Westfeld M

Patient Preference and Adherence 2014, 8:1713-1720

Published Date: 12 December 2014

Cross-linked acrylic hydrogel for the controlled delivery of hydrophobic drugs in cancer therapy

Deepa G, Thulasidasan AK, Anto RJ, Pillai JJ, Kumar GS

International Journal of Nanomedicine 2012, 7:4077-4088

Published Date: 27 July 2012

Crystallization after intravitreal ganciclovir injection

Pitipol Choopong, Nattaporn Tesavibul, Nattawut Rodanant

Clinical Ophthalmology 2010, 4:709-711

Published Date: 14 July 2010