Inhibition of cancer cell proliferation by adenosine triphosphate-triggered codelivery system of p53 gene and doxorubicin
Keywords:
adenosine triphosphate-responsive aptamer, doxorubicin, p53 gene, codelivery, synergistic effectAbstract
The codelivery of drugs and genes by stimuli-responsive nanocarriers is a promising strategy for achieving an effective cancer treatment. In this study, an adenosine triphosphate (ATP)-responsive nanosystem was constructed to codeliver doxorubicin (DOX) and p53 gene based on an ATP-triggered aptamer and polyethyleneimine (PEI). In this system, DOX interacts with the GC-rich motif of duplex formed by the aptamer and its cDNA sequence. Then, a ternary nanocomplex DOX-Duplex/PEI/p53 was constructed using cationic carrier PEI25K for facilitating the intracellular delivery and release of p53 gene and DOX. The DOX-Duplex/PEI/p53 nanocomplex was found to possess an efficient anticancer effect, which was attributed to the ability of the system to trigger cell apoptosis and meanwhile block the cell cycle at G2 phase. The favorable antiproliferative effect was found to be associated with the rapid DOX and p53 gene release in response to the intracellular ATP concentration and the synergistic effect of therapeutic drug and gene.
References
Gandhi L, Rodriguez-Abreu D, Gadgeel S, et al., 2018, Pembrolizumab Plus Chemotherapy in Metastatic Non-small-cell Lung Cancer. N Engl J Med, 378:2078-92. DOI 10.1056/NEJMoa1801005.
Benoist S, Nordlinger B, 2009, The Role of Preoperative Chemotherapy in Patients with Resectable Colorectal Liver Metastases. Ann Surg Oncol, 16:2385-90. DOI 10.1245/ s10434-009-0492-7.
Dean M, Fojo T, Bates S, 2005, Tumour Stem Cells and Drug Resistance. Nat Rev Cancer, 5:275-84. DOI 10.1038/ nrc1590.
Naldini L, 2015, Gene Therapy Returns to Centre Stage. Nature, 526:351-60. DOI 10.1038/nature15818.
Schuler M, Herrmann R, de Greve J L, et al., 2001, Adenovirus-mediated Wild-Type p53 Gene Transfer in Patients Receiving Chemotherapy for Advanced Non-small-cell Lung Cancer: Results of a Multicenter Phase II Study. J Clin Oncol, 19:1750-8. DOI 10.1200/ JCO.2001.19.6.1750.4
Swisher SG, Roth JA, Komaki R, et al., 2003, Induction of p53-regulated Genes and Tumor Regression in Lung Cancer Patients after Intratumoral Delivery of Adenoviral p53 (INGN 201) and Radiation Therapy. Clin Cancer Res, 9:93-101.
Wang Y, Gao S, Ye WH, et al., 2006, Co-delivery of Drugs and DNA from Cationic Core-shell Nanoparticles Self-assembled from a Biodegradable Copolymer. Nat Mater, 5:791-6. DOI 10.1038/nmat1737.
Wei R, Cheng L, Zheng M, et al., 2012, Reduction-responsive Disassemblable Core-cross-linked Micelles Based on Poly(ethylene glycol)-b-poly(N- 2-hydroxypropyl methacrylamide)-lipoic Acid Conjugates for Triggered Intracellular Anticancer Drug Release. Biomacromolecules, 13:2429-38. DOI 10.1021/bm3006819.
Yang Q, Wang S, Fan P, et al., 2005, pH-responsive Carrier System Based on Carboxylic Acid Modified Mesoporous Silica and Polyelectrolyte for Drug Delivery. Chem Mater, 17:5999-6003. DOI 10.1021/cm051198v.
Patel K, Angelos S, Dichtel WR, et al., 2008, Enzyme-responsive Snap-top Covered Silica Nanocontainers. J Am Chem Soc, 130:2382-3. DOI 10.1021/ja0772086.
Lin HM, Wang WK, Hsiung PA, et al., 2010, Light-sensitive Intelligent Drug Delivery Systems of Coumarin-modified Mesoporous Bioactive Glass. Acta Biomater, 6:3256-63. DOI 10.1016/j.actbio.2010.02.014.
Needham D, Dewhirst MW, 2001, The Development and Testing of a New Temperature-sensitive Drug Delivery System for the Treatment of Solid Tumors. Adv Drug Deliv Rev, 53:285-305. DOI 10.1016/S0169-409X(01)00233-2.
Tang X, Li Q, Liang X, et al., 2019, Inhibition of Proliferation and Migration of Tumor Cells Through Lipoic Acid-modified Oligoethylenimine-mediated p53 Gene Delivery. New J Chem, 43:2758-65. DOI 10.1039/c8nj05368e.
Souris JS, Lee CH, Cheng SH, et al., 2010, Surface Charge-mediated Rapid Hepatobiliary Excretion of Mesoporous Silica Nanoparticles. Biomaterials, 31:5564-74. DOI 10.1016/j.biomaterials.2010.03.048.
Ke CJ, Su TY, Chen HL, et al., 2011, Smart Multifunctional Hollow Microspheres for the Quick Release of Drugs in Intracellular Lysosomal Compartments. Angew Chem Int Ed, 50:8086-9. DOI 10.1002/anie.201102852.
Wang Y, Chen J, Liang X, et al., 2017. An ATP-responsive Codelivery System of Doxorubicin and miR- 34a to Synergistically Inhibit Cell Proliferation and Migration. Mol Pharm, 14:2323-32. DOI 10.1021/acs. molpharmaceut.7b00184.
Lu S, Zhao F, Zhang Q, et al., 2018. Therapeutic Peptide Amphiphile as a Drug Carrier with ATP-triggered Release for Synergistic Effect, Improved Therapeutic Index, and Penetration of 3D Cancer Cell Spheroids. Int J Mol Sci, 19:2773. DOI 10.3390/ijms19092773.
Mo R, Jiang T, DiSanto R, et al., 2014. ATP-triggered Anticancer Drug Delivery. Nat Commun, 5:3364. DOI 10.1038/ncomms4364.
Wang GH, Huang GL, Zhao Y, et al., 2016. ATP Triggered Drug Release and DNA co-delivery Systems Based on ATP Responsive Aptamers and Polyethylenimine Complexes. J Mater Chem B, 4:3832-41. DOI 10.1039/C5TB02764K.
Zhang J, Wu D, Xing Z, et al., 2015. N-Isopropylacrylamide-modified polyethylenimine-mediated p53 Gene Delivery to Prevent the Proliferation of Cancer Cells. Colloids Surf B Biointerfaces, 129:54-62. DOI 10.1016/j. colsurfb.2015.03.032.
Xing Z, Gao S, Duan Y, et al., 2015. Delivery of DNAzyme Targeting Aurora Kinase A to Inhibit the Proliferation and Migration of Human Prostate Cancer. Int J Nanomed, 10:5715-27. DOI 10.2147/IJN.S90559.
Leist M, Single B, Castoldi AF, et al., 1997. Intracellular Adenosine Triphosphate (ATP) Concentration: A Switch in the Decision Between Apoptosis and Necrosis. J Exp Med, 185:1481-6. Doi 10.1084/jem.185.8.1481.
Gribble FM, Loussouarn G, Tucker SJ, et al., 2000. A Novel Method for Measurement of Submembrane ATP Concentration. J Biol Chem, 275:30046-9. DOI 10.1074/ jbc.M001010200.
Gorman MW, Feigl EO, Buffington CW, 2007. Human Plasma ATP Concentration. Clin Chem, 53:318-25. DOI 10.1373/clinchem.2006.076364.
Zhang J, Wang Y, Chen J, et al., 2017. Inhibition of Cell Proliferation through an ATP-responsive Co-delivery System of Doxorubicin and Bcl-2 siRNA. Int J Nanomed, 12:4721-32. DOI 10.2147/IJN.S135086.
Downloads
Published
Issue
Section
License
Copyright (c) 2019 Yong Liu, Xinxin Shao, Zhiyuan Shi, Quanshun Li
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
