Near-infrared light triggered photodynamic therapy in combination with gene therapy using upconversion nanoparticles for effective cancer cell killing

Abstract

Upconversion nanoparticles (UCNPs) have drawn much attention in cancer imaging and therapy in recent years. Herein, we for the first time report the use of UCNPs with carefully engineered surface chemistry for combined photodynamic therapy (PDT) and gene therapy of cancer. In our system, positively charged NaGdF4:Yb,Er UCNPs with multilayered polymer coatings are synthesized via a layer by layer strategy, and then loaded simultaneously with Chlorin e6 (Ce6), a photosensitizing molecule, and small interfering RNA (siRNA), which targets the Plk1 oncogene. On the one hand, under excitation by a near-infrared (NIR) light at 980 nm, which shows greatly improved tissue penetration compared with visible light, cytotoxic singlet oxygen can be generated via resonance energy transfer from UCNPs to photosensitizer Ce6, while the residual upconversion luminescence is utilized for imaging. On the other hand, the silencing of Plk1 induced by siRNA delivered with UCNPs could induce significant cancer cell apoptosis. As the result of such combined photodynamic and gene therapy, a remarkably enhanced cancer cell killing effect is realized. Our work thus highlights the promise of UCNPs for imaging guided combination therapy of cancer.

Size Control of Nearly Monodisperse β-NaGdF4 Particles Prepared from Small α-NaGdF4 Nanocrystals

“…Nanoparticles based on the NaGdF 4 host lattice are being investigated for a variety of applications such as magnetic resonance imaging (MRI) [1][2][3][4][5][6][7][8][9] , multimodal biological labelling/sensing and imaging, 10-21 photodynamic therapy, 10,[22][23][24] spectral conversion in solar cells, 25,26 and nanothermometers. 27,28 NaGdF 4 and other NaREF 4 nanocrystals (RE = rare earth) are often prepared in oleic acid based solvent mixtures yielding very narrow particle size distributions.…”

Synthesis and characterization of biologically stable, doped LaF3 nanoparticles co-conjugated to PEG and photosensitizers

“…If the absorption spectrum of the photosensitizer overlaps with the emission spectrum of the nanoparticle, the dye should produce singlet oxygen as in PDT. Several articles have also been published on the conjugation of photosensitizers to upconverting nanoparticles, and their indirect activation via infrared excitation of the nanoparticle [22][23][24][25][26][27][28] . The alternative approach of using downconverting nanoparticles has also been investigated, although not as thoroughly 29,30 .…”

Upconversion Nanoparticles for Light-Activated Therapy

“…Owing to the existence of Gd 3+ , these nanoparticles could serve as a T 1 MR contrasting agent. Very recently, they demonstrated the synergistic anticancer effect of PDT and gene therapy [92]. In this study, NaGdF 4 :Yb/Er UCNPs were functionalized via LbL coating of counter-charged polymers and then loaded with Ce6 via hydrophobic interaction.…”