Journal
PHARMACEUTICAL RESEARCH
Volume 31, Issue 10, Pages 2796-2809Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11095-014-1377-4
Keywords
Cancer therapeutics; EphA2; Imaging; Nanoparticles; Tumor targeted delivery
Funding
- NCI NIH HHS [R21 CA175618, SC1 CA161676] Funding Source: Medline
- NIMHD NIH HHS [P20 MD006738] Funding Source: Medline
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Purpose Evaluation of tumor targeting pegylated EphA2 peptide coated nanoparticles (ENDDs) of a novel anticancer agent DIM-C-pPhC(6)H(5) (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 MXFX 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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