Abstract
Mesoporous silica nanoparticles (MSNs) with large surface area, tunable pore size, and low toxicity can act as suitable vehicles for drug and gene delivery. An MSN/DNA/PEI complex delivery system was prepared by using MSNs to hold plasmid DNA coated with polyethyleneimine (PEI), and the dry powder formulation was produced by freeze-drying with trehalose as lyoprotectant. The MSN/DNA/PEI complexes successfully enhanced the gene expression with about 1.5-fold higher efficiency as compared with the control, and even better effects and lower toxicity were achieved at lower content of PEI. Also, this gene delivery system showed nearly sixfold higher efficiency in the serum-containing condition than the control, so further application of these vehicles in vivo is highly appreciated. Besides, the trehalose containing lyophilized formulation could hold the availability for at least 4 months of storing at room temperature, presenting the potential for industrial production and transportation of gene therapy.
Similar content being viewed by others
References
Cross D, Burmester JK. Gene therapy for cancer treatment: past, present and future. Clin Med Res. 2006;4(3):218–27.
McCormick F. Cancer gene therapy: fringe or cutting edge? Nat Rev Cancer. 2001;1(2):130–41.
Thomas CE, Ehrhardt A, Kay MA. Progress and problems with the use of viral vectors for gene therapy. Nat Rev Genet. 2003;4(5):346–58.
De Smedt SC, Demeester J, Hennink WE. Cationic polymer based gene delivery systems. Pharm Res. 2000;17(2):113–26.
Panyam J, Labhasetwar V. Biodegradable nanoparticles for drug and gene delivery to cells and tissue. Adv Drug Deliv Rev. 2012;55:329–47.
Zhang X-Q, Chen M, Lam R, Xu X, Osawa E, Ho D. Polymer-functionalized nanodiamond platforms as vehicles for gene delivery. ACS Nano. 2009;3(9):2609–16.
Vivero‐Escoto JL, Slowing II, Trewyn BG, Lin VSY. Mesoporous silica nanoparticles for intracellular controlled drug delivery. Small. 2010;6(18):1952–67.
Tang F, Li L, Chen D. Mesoporous silica nanoparticles: synthesis, biocompatibility and drug delivery. Adv Mater. 2012;24(12):1504–34. doi:10.1002/adma.201104763.
Chen AM, Zhang M, Wei D, Stueber D, Taratula O, Minko T, et al. Co-delivery of doxorubicin and Bcl-2 siRNA by mesoporous silica nanoparticles enhances the efficacy of chemotherapy in multidrug-resistant cancer cells. Small. 2009;5(23):2673–7. doi:10.1002/smll.200900621.
Meng H, Liong M, Xia T, Li Z, Ji Z, Zink JI, et al. Engineered design of mesoporous silica nanoparticles to deliver doxorubicin and P-glycoprotein siRNA to overcome drug resistance in a cancer cell line. ACS Nano. 2010;4(8):4539–50.
Xia T, Kovochich M, Liong M, Meng H, Kabehie S, George S, et al. Polyethyleneimine coating enhances the cellular uptake of mesoporous silica nanoparticles and allows safe delivery of siRNA and DNA constructs. ACS Nano. 2009;3(10):3273–86.
Wang X, Masse S, Laurent G, Hélary C, Coradin T. Impact of polyethylenimine conjugation mode on the cell transfection efficiency of silica nanovectors. Langmuir. 2015;31(40):11078–85.
Buchman YK, Lellouche E, Zigdon S, Bechor M, Michaeli S, Lellouche J-P. Silica nanoparticles and polyethyleneimine (PEI)-mediated functionalization: a new method of PEI covalent attachment for siRNA delivery applications. Bioconjug Chem. 2013;24(12):2076–87.
Shen J, Kim H-C, Su H, Wang F, Wolfram J, Kirui D, et al. Cyclodextrin and polyethylenimine functionalized mesoporous silica nanoparticles for delivery of siRNA cancer therapeutics. Theranostics. 2014;4(5):487–97.
Yu M, Niu Y, Yang Y, Hartono SB, Yang J, Huang X, et al. An approach to prepare polyethylenimine functionalized silica-based spheres with small size for siRNA delivery. ACS Appl Mater Interfaces. 2014;6(18):15626–31.
Kircheis R, Wightman L, Wagner E. Design and gene delivery activity of modified polyethylenimines. Adv Drug Deliv Rev. 2001;53(3):341–58.
Yamazaki Y, Nango M, Matsuura M, Hasegawa Y, Hasegawa M, Oku N. Polycation liposomes, a novel nonviral gene transfer system, constructed from cetylated polyethylenimine. Gene Ther. 2000;7(13):1148–55.
Wu H, Pan S, Chen M, Wu Y, Wang C, Wen Y, et al. A serum-resistant polyamidoamine-based polypeptide dendrimer for gene transfection. Biomaterials. 2011;32(6):1619–34.
Lin C, Zhong Z, Lok MC, Jiang X, Hennink WE, Feijen J, et al. Novel bioreducible poly (amido amine) s for highly efficient gene delivery. Bioconjug Chem. 2007;18(1):138–45.
Pietersz GA, Tang C-K, Apostolopoulos V. Structure and design of polycationic carriers for gene delivery. Mini-Rev Med Chem. 2006;6(12):1285–98.
Pan S, Cao D, Huang H, Yi W, Qin L, Feng M. A serum-resistant low-generation polyamidoamine with PEI 423 outer layer for gene delivery vector. Macromol Biosci. 2013;13(4):422–36.
Sameti M, Bohr G, Kumar MR, Kneuer C, Bakowsky U, Nacken M, et al. Stabilisation by freeze-drying of cationically modified silica nanoparticles for gene delivery. Int J Pharm. 2003;266(1):51–60.
Crowe JH, Hoekstra FA, Crowe LM. Anhydrobiosis. Annu Rev Physiol. 1992;54(1):579–99.
Lu J, Li Z, Zink JI, Tamanoi F. In vivo tumor suppression efficacy of mesoporous silica nanoparticles-based drug-delivery system: enhanced efficacy by folate modification. Nanomed Nanotechnol Biol Med. 2012;8(2):212–20. doi:10.1016/j.nano.2011.06.002.
Quan G, Pan X, Wang Z, Wu Q, Li G, Dian L, et al. Lactosaminated mesoporous silica nanoparticles for asialoglycoprotein receptor targeted anticancer drug delivery. J Nanobiotechnol. 2015;13(1):7.
Benezra M, Penate-Medina O, Zanzonico PB, Schaer D, Ow H, Burns A, et al. Multimodal silica nanoparticles are effective cancer-targeted probes in a model of human melanoma. J Clin Invest. 2011;121(7):2768.
Rosenholm JM, Mamaeva V, Sahlgren C, Lindén M. Nanoparticles in targeted cancer therapy: mesoporous silica nanoparticles entering preclinical development stage. Nanomed Nanotechnol Biol Med. 2012;7(1):111–20.
Allison SD, Anchordoquy TJ. Maintenance of nonviral vector particle size during the freezing step of the lyophilization process is insufficient for preservation of activity: insight from other structural indicators. J Pharm Sci. 2001;90(10):1445–55.
Allison SD, Molina MC, Anchordoquy TJ. Stabilization of lipid/DNA complexes during the freezing step of the lyophilization process: the particle isolation hypothesis. Biochim Biophys Acta Biomembr. 2000;1468(1):127–38.
Acknowledgments
The authors appreciate the financial support from the National Natural Science Foundation of China (81473155).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Zhang, X., Zhang, J., Quan, G. et al. The Serum-Resistant Transfection Evaluation and Long-Term Stability of Gene Delivery Dry Powder Based on Mesoporous Silica Nanoparticles and Polyethyleneimine by Freezing-Drying. AAPS PharmSciTech 18, 1536–1543 (2017). https://doi.org/10.1208/s12249-016-0617-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1208/s12249-016-0617-9