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Three-photon imaging using defect-induced photoluminescence in biocompatible ZnO nanoparticles

Authors Raghavendra AJ, Gregory WE, Slonecki TJ, Dong Y, Persaud I, Brown JM, Bruce TF, Podila R

Received 10 February 2018

Accepted for publication 25 April 2018

Published 23 July 2018 Volume 2018:13 Pages 4283—4290

DOI https://doi.org/10.2147/IJN.S165201

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Alexander Kharlamov

Peer reviewer comments 2

Editor who approved publication: Dr Thomas J Webster


Achyut J Raghavendra,1 Wren E Gregory,1 Tyler J Slonecki,2 Yongchang Dong,1 Indushekhar Persaud,3 Jared M Brown,3 Terri F Bruce,2 Ramakrishna Podila1,4

1Laboratory of Nano-Biophysics, Department of Physics and Astronomy, Clemson Nanomaterials Institute, Clemson University, Clemson, SC, USA; 2Clemson Light Imaging Facility, Clemson University, Clemson, SC, USA; 3Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado-Anschutz Medical Campus, Aurora, CO, USA; 4Clemson University School of Health Research and COMSET, Clemson University, Clemson, SC, USA

Background: Although optical spectroscopy promises improved lateral resolution for cancer imaging, its clinical use is seriously impeded by background fluorescence and photon attenuation even in the so-called two-photon absorption (2PA) imaging modality. An efficient strategy to meet the clinical cancer imaging needs, beyond what two-photon absorption (2PA) offers, is to use longer excitation wavelengths through three-photon absorption (3PA). A variety of fluorescent dyes and nanoparticles (NPs) have been used in 3PA imaging. However, their non-linear 3PA coefficient is often low necessitating high excitation powers, which cause overheating, photodamage, and photo-induced toxicity. Doped wide band gap semiconductors such as Mn:ZnS NPs have previously been used for 3PA but suffer from poor 3PA coefficients.
Methods: Here, we prepared ZnO NPs with intrinsic defects with high 3PA coefficients using a polyol method. We functionalized them with peptides for selective uptake by glioblastoma U87MG cells and used breast cancer MCF-7 cells as control for 3PA studies. Uptake was measured using inductively coupled plasma-mass spectrometry. Biocompatibility studies were performed using reactive oxygen species and cell viability assays.
Results: We demonstrate that ZnO NPs, which have a band gap of 3.37 eV with an order of magnitude higher 3PA coefficients, can facilitate the use of longer excitation wavelengths 950–1,100 nm for bioimaging. We used the presence intrinsic defects (such as O interstitials and Zn vacancies) in ZnO NPs to induce electronic states within the band gap that can support strong visible luminescence 550–620 nm without the need for extrinsic doping. The peptide functionalization of ZnO NPs showed selective uptake by U87MG cells unlike MCF-7 cells without the integrin receptors. Furthermore, all ZnO NPs were found to be biocompatible for 3PA imaging.
Conclusion: We show that defect-induced luminescence 550–620 nm in ZnO NPs (20 nm) due to 3PA at longer excitation (975 nm) can be used for 3PA imaging of U87MG glioblastoma cells with lower background noise.

Keywords: three-photon imaging, ZnO nanoparticles, defects, photoluminescence

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