Near-IR photoactivation using mesoporous silica–coated NaYF4:Yb,Er/Tm upconversion nanoparticles

Abstract

Photoactivation is a process in which light is used to 'activate' photolabile therapeutics. As a therapeutic strategy, its advantages are that it is noninvasive and that a high degree of spatial and temporal control is possible. However, conventional photoactivation techniques are hampered by the limited penetration depth of the UV and visible lights to which the photosensitive compounds are responsive. Here we describe a protocol for the use of upconversion nanoparticles (UCNs) as light transducers to convert deeply penetrating near-infrared (NIR) light to UV-visible wavelengths matching that of the absorption spectrum of photosensitive therapeutics. This allows the use of deep-penetrating and biologically friendly NIR light instead of low-penetrating and/or toxic visible or UV lights for photoactivation. In this protocol, we focus on two photoactivation applications: photodynamic therapy (PDT) and photoactivated control of gene expression. We describe how to prepare and characterize the UCNs, as well as how to check their function in biochemical assays and in cells. For both applications, the UCNs are coated with mesoporous silica for easy loading of the therapeutics. For PDT, the UCNs are coated with polyethylene glycol (PEG) for stabilization and folic acid for tumor targeting and then loaded with photosensitizers that would be expected to kill cells by singlet oxygen production; the nanoparticles are injected intravenously. For photoactivated control of gene expression, knockdown of essential tumor genes is achieved using UCNs loaded with caged nucleic acids, which are injected intratumorally. The whole process from nanoparticle synthesis to animal studies takes ∼36 d.

Nanoscale mapping of ZnO–TiO2 up-conversion phosphor containing Yb3+ and Er3+

“…Yb-Er and Yb-Tm type materials are often used for co-doping. For the host material, halides such as NaYF 4 are often used to obtain high emission intensities [16][17][18][19][20][21][22][23][24][25], but these halides have problematic hygroscopicity. Using a metal oxide as a host material is a possible alternative, as metal oxides such as ZnO and TiO 2 are highly stable in the ambient atmosphere.…”

Glutathione Mediated Size‐Tunable UCNPs‐Pt(IV)‐ZnFe2O4 Nanocomposite for Multiple Bioimaging Guided Synergetic Therapy

“…Concerning above‐mentioned issues, upconversion nanoparticles (UCNPs) have received much attention due to the capability of converting longer wavelength irradiation (NIR) into the shorter wavelength light (UV or visible light) . Based on this character, on account of multiphoton absorption of NIR light, Yb/Tm‐codoped UCNPs can be used as an efficient UV–vis source, triggering PDT effect and toxic •OH to kill cancer cells . In addition, the UCNPs containing Yb or Gd could be served as excellent CT contrast agents owning to their high atomic and strong X‐ray attenuation, which are of great significant for cancer diagnosis .…”

Förster Resonance Energy Transfer‐Activated Processes in Smart Nanotheranostics Fabricated in a Sustainable Manner

“…Changing the doping ion pair to Er 3 + /Yb 3 + furthere xtends the list of possible light-sensitive drugs to be conjugated with UCNPs.I nf act, av ery interesting approachw as proposed by Gao et al [19] who used stem cells as aU CNPs coating fore nhanced tumor targetingf unctionalities, whereas the conjugation with Bengal Rose (BR) allowed fore fficient energy-transfer-based photodynamic therapy (PDT) upon 980 nm excitation.I nteractionb etween Er 3 + /Yb 3 + -dopedU CNPs and BR was also applied for NIR-triggered PDT in neuroendocrine tumors. [22][23][24] Thosea pproaches were, however, focused on the surfacem odification of single UCNPs for conjugation with PS agents, cytostatic drugs, and targeting molecules. The obtained hybrid NPs were additionally functionalized with hyaluronica cidf or targeted cancerc ell delivery.L ikewise, folic acid (FA) functionalized polymers or nucleic acids were proposed as tumor targetingl igandsf or UCNPs.…”

“…The obtained hybrid NPs were additionally functionalized with hyaluronica cidf or targeted cancerc ell delivery.L ikewise, folic acid (FA) functionalized polymers or nucleic acids were proposed as tumor targetingl igandsf or UCNPs. [22][23][24] Thosea pproaches were, however, focused on the surfacem odification of single UCNPs for conjugation with PS agents, cytostatic drugs, and targeting molecules. Unfortunately,t his can result in unwanted material loss, aggregation,u nexpected interactions between organic molecules at the NPs surface, and finally in the decrease in UC emission intensity and luminescence lifetime shortening.…”