Cellular Uptake and Localization of Novel NSCLC Penetrating Peptide with Neuropilin-1 Binding Motif
Abstract
To synthesize and study the specific binding affinity of tumor-penetrating peptide YCCS to non-small cell lung carcinoma (NSCLC) cells in vitro. Methods YCCS peptide was designed by fusing the neuropilin-1 (NRP-1) binding sequence and NSCLC binding peptide CS. YCCS peptide was synthesized and fluorescent labeled with N-terminal FITC.NRP-1 positive human NSCLC cell A549, NRP-1 positive human breast cancer cell MDA-MB-231, normal human bronchial epithelium HBE135-E6E7 and human liver cell HL-7702 were incubated respectively，then we observed the specific binding affinity of tumor-penetrating peptide YCCS to NSCLC cells. Results After treated with 5 μmol/L peptide, significant fluorescent signals of FITC-YCCS peptide were demonstrated only in NSCLC A549 cells but marginal captured signal in MDA-MB-231, normal human HBE135-E6E7 or HL-7702 cells, which revealed specific NSCLC cells binding affinity. In 20 μmol/L treated group, non-specific binding were found in MDA-MB-231 and HL-7702 cells. Conclusion The results of this novel designed YCCS peptide indicated a promising strategy for improving tumor penetrating with delivery capability of drugs to NSCLC A549 cells when treated with 5 μmol/L peptide.
Keywords: Non-small cell lung carcinoma, Tumor-targeting, Neuropilin-1, C-end rule motif peptide
Full Text:
PDFReferences
Jubb AM, Strickland LA, Liu SI), et al. Neuropilin-1 expression in cancer and development. J Pathol, 2012-226( 1): 50-60.
Hllis LM. The role of neuropilins in cancer. Mol Cancer Ther, 2006*5(5):1099-1107.
Hong TM, Chen YL. Wu YY. et al. Targeting neuropilin 1 as an antitumor strategy in lung cancer. Clin Cancer Res,2007; 13 (16)=4759-4768.
Kamiya T. Kawakami, Abe Y, et al. The preserved expression of neuropilin ( NRP) 1 contributes to a better prognosis in colon cancer. Oncol Rep,2006? 15(2):369-373. Kreuter M. Woelke K. Bicker R. et al. Correlation of neuropilin-1 overexpression to survival in acute myeloid leukemia. Leukemia,2006;20( 11); 1950-1954.
Kawakami T, Tokunaga T, Hatanaka H. et al. Neuropilin 1 and neuropilin 2 co-expression is significantly correlated with increased vascularity and poor prognosis in nonsmall cell lung carcinoma. Cancer,2002;95(10):2196-2201.
TeesaluT, Sugahara KN, Kotamraju VR, et al. С-end rule peptides mediate neuropilin-1-dependent cell, vascular, and tissue penetration. Proc Natl Acad Sci U S Л.2009; 106(38): 16157-16162.
Haspel N. Zanuy I). Nussinov R, et al. Binding of a C-end rule peptide to the neuropilin-1 receptor; a molecular modeling approach. Biochemistry,2011 ;50( 10); 1755-1762.
Sugahara KN. Teesalu T. Karmali PP. et al. Tissue- penetrating delivery of compounds and nanoparticles into tumors. Cancer Cell.2009} 16(6):510-520.
Sugahara KN. Teesalu T. Karmali PP. etal. Coadministration of a tumor-penetrating peptide enhances the efficacy of cancer drugs. Science.2010;328(5981); 1031-1035.
Sharma A. Kapoor P. Gautam A. et al. Computational approach for designing tumor homing peptides. Sci Rep. 2013; 3:1607. doi: 10. 1038/srep01607.
Zhu Z. Xie C. Liu Q« et al. The effect of hydrophilic chain length and iRGD on drug delivery from poly ( epsilon- caprolactone )-poly ( N-vinylpyrrolidone ) nanoparticles. Biomaterials.2011 ;32(35):9525-9535.
Puig-Saus C. Rojas LA. Laborda K. et al. iRGD tumor- penetrating peptide-modified oncolytic adenovirus shows enhanced tumor transduction, intratumoral dissemination and antitumor efficacy. Gene Ther.2014 ;21 (8): 767-774.
Cai H. Yang H. Xiang B. etal. Selective apoptotic killing of solid and hematologic tumor cells by bombesin-targeted delivery of mitochondria-disrupiing peptides. Mol Pharm. 2010; 7 (2): 586-596.
Yang H. Liu S. Cai H. et al. Chondroitin sulfate as a molecular portal that preferentially mediates the apoptotic killing of tumor cells by penet rat in-directed mitochondria- disrupting peptides. J Biol Chem,2010;285(33) :25666-25676.
Laakkonen P. Porkka K. Hoffman JA. Et al. A tumor-homing peptide with a targeting specificity related to lymphatic vessels. Nat Med,2002;8(7): 751-755.
Laakkonen P. Akerman MK. Biliran H. et al. Antitumor activity of a homing peptide that targets tumor lymphatics and tumor cells. Proc Natl Acad Sci U S A. 2004; 101 (25): 9381- 9386.
Alberici L. Roth L. Sugahara KN. et al. De novo design of a tumor-penetrating peptide. Cancer Res.2013;73(2):804-812.
Hu Q. Gu G. Liu Z. et al. F3 peptide-functionalized PEG- PLA nanoparticles со-administrated with tLyp-1 peptide for anti-glioma drug delivery. Biomaterials, 2013; 34 ( 4 ): 1135- 1145.
Yang ZZ. Li JQ. Wang ZZ, et al. Tumor-targeting dual peptides-modified cationic liposomes for delivery of siRNA and docetaxel to gliomas. Biomaterials.2014 ;35(19):5226-5239.
He X. Na MH. Kim JS. et al. A novel peptide probe for imaging and targeted delivery of liposomal doxorubicin to lung tumor. Mol Pharm,2011 ;8(2):430-438.
Wei D. I-i J. Shen M, et al. Cellular production of n-3 PUFAs and reduction of n-6-to-n-3 ratios in the pancreatic p-cells and islets enhance insulin secretion and confer protection against cytokin-induced cell death. Diabetes.2010;59(2) :471-478.
Lin Y, Sun X. Qiu, et al. Exposure to bisphenol A induces dysfunction of insulin secretion and apotosis through the damage of mitochonfria in rat insulinoma (INS-1 ) cells. Cell Death Dis. 2013 Jan 17;4:e460. doi: 10. 1038/cddis. 2012. 206.
Motoshige H. Oyama K. Takahashi K. et al. Involvement of phosphatidylinositol З-kinase/Akt pathway in gemcitabine- induced apoptosis-like cell death in insulinoma cell line INS-1. Biol Pharni Bull.2012;35( 11) = 1932-1940.
Ruszkowska-Ciastek B. Sokup A. Socha MW, et al. A preliminary evaluation of VEGF-A. VEGFR1 and VEGFR2 in patients with well-controlled type 2 diabetes mellitus. J Zhejiang Univ Sci B.2014; 15(6) =575-581.
Zorena K. My sliwska J. My sliwiec M. et al. Association between vascular endothelial growth factor and hypertension in children and adolescents type I diabetes mellitus. J Hum Hypertenst 2010;24( 11): 755-762.
Refbacks
- There are currently no refbacks.
