pubmed.ncbi.nlm.nih.gov

Targeted lung cancer therapy: preparation and optimization of transferrin-decorated nanostructured lipid carriers as novel nanomedicine for co-delivery of anticancer drugs and DNA - PubMed

  • ️Thu Jan 01 2015

Targeted lung cancer therapy: preparation and optimization of transferrin-decorated nanostructured lipid carriers as novel nanomedicine for co-delivery of anticancer drugs and DNA

Zhenyu Shao et al. Int J Nanomedicine. 2015.

Abstract

Purpose: Nanostructured lipid carriers (NLC) represent an improved generation of lipid nanoparticles. They have specific nanostructures to accommodate drugs/genes, and thus achieve higher loading capacity. The aim of this study was to develop transferrin (Tf)-decorated NLC as multifunctional nanomedicine for co-delivery of paclitaxel (PTX) and enhanced green fluorescence protein plasmid.

Methods: Firstly, Tf-conjugated ligands were synthesized. Secondly, PTX- and DNA-loaded NLC (PTX-DNA-NLC) was prepared. Finally, Tf-containing ligands were used for the surface decoration of NLC. Their average size, zeta potential, drug, and gene loading were evaluated. Human non-small cell lung carcinoma cell line (NCl-H460 cells) was used for the testing of in vitro transfection efficiency, and in vivo transfection efficiency of NLC was evaluated on mice bearing NCl-H460 cells.

Results: Tf-decorated PTX and DNA co-encapsulated NLC (Tf-PTX-DNA-NLC) were nano-sized particles with positive zeta potential. Tf-PTX-DNA-NLC displayed low cytotoxicity, high gene transfection efficiency, and enhanced antitumor activity in vitro and in vivo.

Conclusion: The results demonstrated that Tf-PTX-DNA-NLC can achieve impressive antitumor activity and gene transfection efficiency. Tf decoration also enhanced the active targeting ability of the carriers to NCl-H460 cells. The novel drug and gene delivery system offers a promising strategy for the treatment of lung cancer.

Keywords: active targeting systems; co-delivery; nanostructured lipid carriers; paclitaxel; transferrin decoration.

PubMed Disclaimer

Figures

Figure 1
Figure 1

Schematic diagram of Tf-PTX-DNA-NLC. Notes: Tf-PTX-DNA-NLC was prepared, firstly, by the formation of PTX-DNA-NLC, and then, Tf-PEG-PE was prepared and was placed onto the surface of PTX-DNA-NLC to obtain Tf-PTX-DNA-NLC. Abbreviations: Tf-PTX-DNA-NLC, transferrin-decorated paclitaxel and deoxyribonucleic acid co-encapsulated nanostructured lipid carriers; PTX-DNA-NLC, paclitaxel- and deoxyribonucleic acid-loaded nanostructured lipid carriers; Tf-PEG-PE, transferrin-conjugated polyethylene glycol-phosphatidylethanolamine.

Figure 2
Figure 2

TEM imaging of different NLC formulations. Notes: PTX-DNA-NLC (A) had a spherical shape. Tf5k-PTX-DNA-NLC (B) and Tf10k-PTX-DNA-NLC (C) had slight, light coats on white, spherical-shaped particles. Abbreviations: NLC, nanostructured lipid carriers; TEM, transmission electron microscopy; PTX-DNA-NLC, paclitaxel- and deoxyribonucleic acid-loaded nanostructured lipid carriers; Tf5k-PTX-DNA-NLC, transferrin-conjugated polyethylene glycol 5000-phosphatidylethanolamine-decorated paclitaxel- and deoxyribonucleic acid-loaded nanostructured lipid carriers; Tf10k-PTX-DNA-NLC, transferrin-conjugated polyethylene glycol 10000-phosphatidylethanolamine-decorated paclitaxel- and deoxyribonucleic acid-loaded nanostructured lipid carriers.

Figure 3
Figure 3

The particle size and zeta potential of different NLC formulations. Notes: The particle size (nm) and zeta potential (mV) of (A) blank NLC, (B) PTX-DNA-NLC, (C) Tf5k-PTX-DNA-NLC, and (D) Tf10k-PTX-DNA-NLC. Abbreviations: NLC, nanostructured lipid carriers; Tf-PTX-DNA-NLC, transferrin-decorated paclitaxel and deoxyribonucleic acid co-encapsulated nanostructured lipid carriers; PTX-DNA-NLC, paclitaxel- and deoxyribonucleic acid-loaded nanostructured lipid carriers; Tf-PEG-PE, transferrin-conjugated polyethylene glycol-phosphatidylethanolamine; Tf5k-PTX-DNA-NLC, transferrin-conjugated polyethylene glycol 5000-phosphatidylethanolamine-decorated paclitaxel- and deoxyribonucleic acid-loaded nanostructured lipid carriers; Tf10k-PTX-DNA-NLC, transferrin-conjugated polyethylene glycol 10000-phosphatidylethanolamine-decorated paclitaxel- and deoxyribonucleic acid-loaded nanostructured lipid carriers.

Figure 4
Figure 4

In vitro drug release profile of different NLC formulations. Notes: The in vitro drug release profile of (A) Tf10k-PTX-DNA-NLC, (B) Tf5k-PTX-DNA-NLC, (C) PTX-DNA-NLC, and (D) Taxol®. Abbreviations: h, hours; NLC, nanostructured lipid carriers; PTX-DNA-NLC, paclitaxel- and deoxyribonucleic acid-loaded nanostructured lipid carriers; Tf5k-PTX-DNA-NLC, transferrin-conjugated polyethylene glycol 5000-phosphatidyle thanol-am ine-decorated paclitaxel- and deoxyribonucleic acid-loaded nanostructured lipid carriers; Tf10k-PTX-DNA-NLC, transferrin-conjugated polyethylene glycol 10000-phosphatidylethanolamine-decorated paclitaxel- and deox yribonucleic acid-loaded nanostructured lipid carriers.

Figure 5
Figure 5

In vitro cytotoxicity of different NLC formulations. Notes: Cell viability tests of Taxol®, PTX-DNA-NLC, Tf5k-PTX-DNA-NLC, and Tf10k-PTX-DNA-NLC were performed at the PTX concentrations of 5, 10, 20, 50, and 100 μM. Blank NLC, blank Tf5k-NLC, and blank Tf10k-NLC were also analyzed as contrast. Tf5k-PTX-DNA-NLC had the highest cytotoxic effect compared with other formulations (P<0.05). Abbreviations: PTX, paclitaxel; NLC, nanostructured lipid carriers; PTX-DNA-NLC, paclitaxel- and deoxyribonucleic acid-loaded nanostructured lipid carriers; Tf5k-PTX-DNA-NLC, transferrin-conjugated polyethylene glycol 5000-phosphatidylethanolamine-decorated paclitaxel- and deoxyribonucleic acid-loaded nanostructured lipid carriers; Tf10k-PTX-DNA-NLC, transferrin-conjugated polyethylene glycol 10000-phosphatidylethanolamine-decorated paclitaxel- and deoxyribonucleic acid-loaded nanostructured lipid carriers.

Figure 6
Figure 6

Effects of different NLC formulations on tumor growth in vivo. Notes: Tumor growth was suppressed to some extent after administration of Taxol®. Tf5k-PTX-DNA-NLC exhibited significantly better tumor regression than Tf10k-PTX-DNA-NLC and PTX-DNA-NLC (P<0.05). Abbreviations: NLC, nanostructured lipid carriers; PTX-DNA-NLC, paclitaxel-and deoxyribonucleic acid-loaded nanostructured lipid carriers; Tf5k-PTX-DNA-NLC, transferrin-conjugated polyethylene glycol 5000-phosphatidylethanolamine-decorated paclitaxel- and deoxyribonucleic acid-loaded nanostructured lipid carriers; Tf10k-PTX-DNA-NLC, transferrin-conjugated polyethylene glycol 10000-phosphatidylethanolamine-decorated paclitaxel- and deoxyribonucleic acid-loaded nanostructured lipid carriers.

Figure 7
Figure 7

Flow cytometry analysis of in vitro gene transfection. Notes: Significantly higher transfection efficiency was observed in Tf5k-PTX-DNA-NLC and Lipo-DNA than other formulations at both 36 hours and 72 hours after transfection (P<0.05). At 36 hours, the transfection efficiency of Tf5k-PTX-DNA-NLC was lower than Lipo-DNA complexes (P<0.05), while higher transfection efficiency was obtained at 72 hours when compared with Lipo-DNA (P<0.05). Tf10k-PTX-DNA-NLC did not exhibit good in vitro gene transfection ability at either 36 or 72 hours. Abbreviations: h, hours; NLC, nanostructured lipid carriers; DNA, deoxyribonucleic acid; Lipo-DNA, Lipofectamine®-DNA complexes; Tf5k-PTX-DNA-NLC, transferrin-conjugated polyethylene glycol 5000-phosphatidylethanolamine-decorated paclitaxel- and deoxyribonucleic acid-loaded nanostructured lipid carriers; Tf10k-PTX-DNA-NLC, transferrin-conjugated polyethylene glycol 10000-phosphatidylethanolamine-decorated paclitaxel- and deoxyribonucleic acid-loaded nanostructured lipid carriers.

Figure 8
Figure 8

Flow cytometry analysis of in vivo gene transfection. Notes: Significantly higher transfection efficiency was observed in Tf5k-PTX-DNA-NLC and Lipo-DNA than other formulations at both 36 hours and 72 hours after transfection (P<0.05). At 36 hours, the transfection efficiency of Tf5k-PTX-DNA-NLC was similar to that of Lipo-DNA complexes, while higher transfection efficiency was obtained at 72 hours when compared with Lipo-DNA (P<0.05). Tf10k-PTX-DNA-NLC did not exhibit good in vivo gene transfection ability at either 36 or 72 hours; the data were indicative of poorer efficiency than data obtained from non-decorated PTX-DNA-NLC. Abbreviations: h, hours; DNA, deoxyribonucleic acid; NLC, nanostructured lipid carriers; Lipo-DNA, Lipofectamine®-DNA complexes; PTX-DNA-NLC, paclitaxel-and deoxyribonucleic acid-loaded nanostructured lipid carriers; Tf5k-PTX-DNA-NLC, transferrin-conjugated polyethylene glycol 5000-phosphatidylethanolamine-decorated paclitaxel- and deoxyribonucleic acid-loaded nanostructured lipid carriers; Tf10k-PTX-DNA-NLC, transferrin-conjugated polyethylene glycol 10000-phosphatidylethanolamine-decorated paclitaxel- and deoxyribonucleic acid-loaded nanostructured lipid carriers.

Similar articles

Cited by

References

    1. Jemal A, Thun MJ, Ries LA, et al. Annual report to the nation on the tatus of cancer, 1975–2005, featuring trends in lung cancer, tobacco use, and tobacco control. J Natl Cancer Inst. 2008;100(23):1672–1694. - PMC - PubMed
    1. Tekade RK, Dutta T, Tyagi A, Bharti AC, Das BC, Jain NK. Surface-engineered dendrimers for dual drug delivery: a receptor up-regulation and enhanced cancer targeting strategy. J Drug Target. 2008;16(10):758–772. - PubMed
    1. Taratula O, Kuzmov A, Shah M, Garbuzenko OB, Minko T. Nanostructured lipid carriers as multifunctional nanomedicine platform for pulmonary co-delivery of anticancer drugs and siRNA. J Control Release. 2013;171(3):349–357. - PMC - PubMed
    1. Kanapathipillai M, Brock A, Ingber DE. Nanoparticle targeting of anti-cancer drugs that alter intracellular signaling or influence the tumor microenvironment. Adv Drug Deliv Rev. 2014;79C–80C:107–118. - PubMed
    1. Hu CM, Zhang L. Nanoparticle-based combination therapy toward overcoming drug resistance in cancer. Biochem Pharmacol. 2012;83(8):1104–1111. - PubMed

MeSH terms

Substances