Phenanthriplatin(iv) conjugated multifunctional up-converting nanoparticles for drug delivery and biomedical imaging

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Journal Article
Journal of Materials Chemistry B, 2018, 6 (31), pp. 5059 - 5068
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© The Royal Society of Chemistry 2018. Platinum-based drugs cisplatin, carboplatin, and oxaliplatin are widely used in the clinical treatment of cancer. However, the clinical applications of platinum-based drugs are greatly limited by the side-effects, lack of selectivity, fast blood clearance, and intrinsic or acquired drug resistance. In this study, we report an anticancer drug delivery system based on phenanthriplatin(iv) (Phen-Pt(iv))-conjugated NaGdF 4 :Yb 3+ /Er 3+ nanoparticles. The upconversion luminescent NaGdF 4 :Yb 3+ /Er 3+ nanoparticles (UCNPs) were further modified with polyethyleneimine (PEI), poly(ethylene glycol) (PEG) and the cancer targeting ligand arginine-glycine-aspartic peptide (RGD), resulting in the formation of water-dispersible and biologically functionalized UCNP@PEI-Phen-Pt-PEG-RGD nanoparticles. The Phen-Pt-conjugated UCNP@PEI-Phen-Pt-PEG-RGD nanoparticles exhibited an obvious cytotoxic effect on Hep-2 cells (Human Laryngeal Carcinoma cell line) via MTT assay. Meanwhile, the endocytosis process of Phen-Pt-conjugated NaGdF 4 :Yb 3+ /Er 3+ nanoparticles by Hep-2 cells was demonstrated through flow cytometry and ICP-MS. In addition, the upconversion luminescence image of UCNP@PEI-Phen-Pt-PEG-RGD taken up by cells shows green emission under 980 nm infrared laser excitation, making the UCNP@PEI-Phen-Pt-PEG-RGD nanocomposites promising candidates as bioimaging agents. Moreover, these UCNPs were further explored for in vitro and in vivo T 1 -weighted magnetic resonance (MR) imaging. The in vivo experiments on mice also confirmed that the Phen-Pt(iv)-conjugated nanoparticles have a relatively high tumor inhibition rate. These results indicate that the multifunctional nanoparticles can be expected to be a platform for simultaneous imaging and cancer therapeutic applications.
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