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EphA2 Targeting Pegylated Nanocarrier Drug Delivery System for Treatment of Lung Cancer

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Abstract

Purpose

Evaluation of tumor targeting pegylated EphA2 peptide coated nanoparticles (ENDDs) of a novel anticancer agent DIM-C-pPhC6H5 (DIM-P) and Docetaxel (DOC) and investigate its antitumor activity and potential for treatment of lung cancer.

Methods

Nanoparticles were prepared with DIM-P and DOC (NDDs) using Nano-DeBEE. ENDDs were prepared by conjugating NDDs with 6His-PEG2K-EphA2 peptide and characterized for physicochemical properties, binding assay, cytotoxicity, cellular uptake studies, drug release and pharmacokinetic parameters. Anti-tumor activity of ENDDs was evaluated using a metastatic H1650 and orthotopic A549 tumor models in nude mice and tumor tissue were analyzed by RT-PCR and immunohistochemistry.

Results

Particle size and entrapment efficiency of ENDDs were 197 ± 21 nm and 95 ± 2%. ENDDs showed 32.5 ± 3.5% more cellular uptake than NDDs in tumor cells. ENDDs showed 23 ± 3% and 26 ± 4% more tumor reduction compared to NDDs in metastatic and orthotopic tumor models, respectively. In-vivo imaging studies using the Care stream MX FX Pro system showed (p < 0.001) 40–60 fold higher flux for ENDDs compared to NDDs at tumor site.

Conclusions

The results emanating from these studies demonstrate anti-cancer potential of DIM-P and the role of ENDDs as effective tumor targeting drug delivery systems for lung cancer treatment.

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Abbreviations

DIM-P:

DIM-C-pPhC6H5

Doc:

Docetaxel

DOGS-NTA-Ni:

1,2-dioleoyl-sn-glycero-3-[(N-(5-amino-1-carboxypentyl) imidodiacetic acid) succinyl nickel salt]

DSC:

Differential Scanning Colorimetry

ENDDs:

EphA2 peptide coated nanoparticles

His:

Histidine

Nano-luc:

Luciferin containing NDDs

Nano-luc-EphA2:

Luciferin containing ENDDs

NCs:

Nanolipidcarriers

NDDs:

Nanoparticles with DIM-P and

NDi:

Nanoparticles with DIM-P

NDo:

Nanoparticles with Doc

NSCLC:

non small cell lung cancer

PEG2K:

Polyethylene Glycol (2,000 daltons)

TPGS:

D-alpha tocopheryl polyethylene glycol 1,000 succinate

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Authors and Affiliations

  1. College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, Florida, 32307, USA

    Apurva R. Patel & Mandip Singh

  2. College of Pharmacy, University of Hawaii at Hilo, Hilo, Hawaii, 96720, USA

    Mahavir Chougule

Authors
  1. Apurva R. Patel
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  2. Mahavir Chougule
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Correspondence to Mandip Singh.

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Figure S1

Binding assay to optimize amount of EphA2 peptide with respect to DOGS-NTA-Ni concentration. Flow cytometry histograms with A) 0 μg of EphA2 peptide, B) 6.25 μg of EphA2 peptide, C) 12.5 of EphA2 peptide μg, D) 25 of EphA2 peptide μg. (GIF 106 kb)

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Patel, A.R., Chougule, M. & Singh, M. EphA2 Targeting Pegylated Nanocarrier Drug Delivery System for Treatment of Lung Cancer. Pharm Res 31, 2796–2809 (2014). https://doi.org/10.1007/s11095-014-1377-4

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  • DOI: https://doi.org/10.1007/s11095-014-1377-4

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