Enhancing the imaging and biosafety of upconversion nanoparticles through phosphonate coating.
Upconversion nanoparticles (UCNPs), which are generated by doping with rare earth (RE) metals, are increasingly used for bioimaging because of the advantages they hold over conventional fluorophores. However, because pristine RE nanoparticles (NPs) are unstable in acidic physiological fluids (e.g., lysosomes), leading to intracellular phosphate complexation with the possibility of lysosomal injury, it is important to ensure that UCNPs are safely designed. In this study, we used commercially available NaYF4:Er/Yb UCNPs to study their stability in lysosomes and simulated lysosomal fluid. We demonstrate that phosphate complexation leads to REPO4 deposition on the particle surfaces and morphological transformation. This leads to a decline in upconversion fluorescence efficiency as well as inducing pro-inflammatory effects at the cellular level and in the intact lung. In order to preserve the imaging properties of the UCNPs as well as improve their safety, we experimented with a series of phosphonate chemical moieties to passivate particle surfaces through the strong coordination of the organophosphates with RE atoms. Particle screening and physicochemical characterization revealed that ethylenediamine tetra(methylenephosphonic acid) (EDTMP) surface coating provides the most stable UCNPs, which maintain their imaging intensity and do not induce pro-inflammatory effects in vitro and in vivo. In summary, phosphonate coating presents a safer design method that preserves and improves the bioimaging properties of UCNPs, thereby enhancing their biological use.
†Division of NanoMedicine, Department of Medicine, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, California 90095, United States.
Ruibin
R
Li
‡California NanoSystems Institute, University of California Los Angeles, 570 Westwood Plaza, Los Angeles, California 90095, United States.
Zhaoxia
Z
Ji
Juyao
J
Dong
‡California NanoSystems Institute, University of California Los Angeles, 570 Westwood Plaza, Los Angeles, California 90095, United States.
Chong Hyun
CH
Chang
‡California NanoSystems Institute, University of California Los Angeles, 570 Westwood Plaza, Los Angeles, California 90095, United States.
Xiang
X
Wang
†Division of NanoMedicine, Department of Medicine, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, California 90095, United States.
Bingbing
B
Sun
†Division of NanoMedicine, Department of Medicine, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, California 90095, United States.
Meiying
M
Wang
†Division of NanoMedicine, Department of Medicine, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, California 90095, United States.
Yu-Pei
YP
Liao
‡California NanoSystems Institute, University of California Los Angeles, 570 Westwood Plaza, Los Angeles, California 90095, United States.
Jeffrey I
JI
Zink
†Division of NanoMedicine, Department of Medicine, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, California 90095, United States.|‡California NanoSystems Institute, University of California Los Angeles, 570 Westwood Plaza, Los Angeles, California 90095, United States.
Andre E
AE
Nel
†Division of NanoMedicine, Department of Medicine, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, California 90095, United States.|‡California NanoSystems Institute, University of California Los Angeles, 570 Westwood Plaza, Los Angeles, California 90095, United States.
Tian
T
Xia
D000818:Animals; D002460:Cell Line; D004871:Erbium / Q000737:chemistry; D005459:Fluorides / Q000737:chemistry; D006801:Humans; D008297:Male; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D057054:Molecular Imaging / Q000009:adverse effects* / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry*; D009943:Organophosphorus Compounds / Q000737:chemistry*; D012449:Safety; D013499:Surface Properties; D015018:Ytterbium / Q000737:chemistry; D015019:Yttrium / Q000737:chemistry
D009943:Organophosphorus Compounds; C525362:sodium yttriumtetrafluoride; C018940:(ethylenedinitrilo)-tetramethylenephosphonic acid; D015019:Yttrium; D004871:Erbium; D015018:Ytterbium; D005459:Fluorides
cell uptake; fluorescence quenching; functionalization; lysosome; nanotoxicity; surface coating