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Toxicol Appl Pharmacol. 2014 Mar 15;275(3):232-43. doi: 10.1016/j.taap.2014.01.012. Epub 2014 Jan 25.

Ligand-conjugated mesoporous silica nanorattles based on enzyme targeted prodrug delivery system for effective lung cancer therapy.

Author information

1
Proteomics and Molecular Cell Physiology Laboratory, Department of Zoology, Bharathiar University, Coimbatore 641 046, TN, India. Electronic address: sundarrajbu09@gmail.com.
2
Proteomics and Molecular Cell Physiology Laboratory, Department of Zoology, Bharathiar University, Coimbatore 641 046, TN, India; Department of Virology, King Institute of Preventive Medicine and Research, Guindy, Chennai 600 032, TN, India.
3
Proteomics and Molecular Cell Physiology Laboratory, Department of Zoology, Bharathiar University, Coimbatore 641 046, TN, India.
4
Proteomics and Molecular Cell Physiology Laboratory, Department of Zoology, Bharathiar University, Coimbatore 641 046, TN, India; Department of Zoology, Periyar University, Salem 636 011, TN, India. Electronic address: skperiyaruniv@gmail.com.

Abstract

Epidermal growth factor receptor antibody (EGFRAb) conjugated silica nanorattles (SNs) were synthesized and used to develop receptor mediated endocytosis for targeted drug delivery strategies for cancer therapy. The present study determined that the rate of internalization of silica nanorattles was found to be high in lung cancer cells when compared with the normal lung cells. EGFRAb can specifically bind to EGFR, a receptor that is highly expressed in lung cancer cells, but is expressed at low levels in other normal cells. Furthermore, in vitro studies clearly substantiated that the cPLA2α activity, arachidonic acid release and cell proliferation were considerably reduced by pyrrolidine-2 loaded EGFRAb-SN in H460 cells. The cytotoxicity, cell cycle arrest and apoptosis were significantly induced by the treatment of pyrrolidine-2 loaded EGFRAb-SN when compared with free pyrrolidine-2 and pyrrolidine-2 loaded SNs in human non-small cell lung cancer cells. An in vivo toxicity assessment showed that silica nanorattles and EGFRAb-SN-pyrrolidine-2 exhibited low systemic toxicity in healthy Balb/c mice. The EGFRAb-SN-pyrrolidine-2 showed a much better antitumor activity (38%) with enhanced tumor inhibition rate than the pyrrolidine-2 on the non-small cell lung carcinoma subcutaneous model. Thus, the present findings validated the low toxicity and high therapeutic potentials of EGFRAb-SN-pyrrolidine-2, which may provide a convincing evidence of the silica nanorattles as new potential carriers for targeted drug delivery systems.

KEYWORDS:

Drug delivery system (DDS); Epidermal growth factor receptor (EGFR); Lung cancer therapy; Pyrrolidine-2; Silica nanorattles; cPLA(2)α activity

PMID:
24467950
DOI:
10.1016/j.taap.2014.01.012
[Indexed for MEDLINE]

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