Conventional photodynamic therapy (PDT) is limited by the penetration depth of visible light needed for its activation. Here we used mesoporous-silica-coated upconversion fluorescent nanoparticles (UCNs) as a nanotransducer to convert deeply penetrating near-infrared light to visible wavelengths and a carrier of photosensitizers. We also used the multicolor-emission capability of the UCNs at a single excitation wavelength for simultaneous activation of two photosensitizers for enhanced PDT. We showed a greater PDT efficacy with the dual-photosensitizer approach compared to approaches using a single photosensitizer, as determined by enhanced generation of singlet oxygen and reduced cell viability. In vivo studies also showed tumor growth inhibition in PDT-treated mice by direct injection of UCNs into melanoma tumors or intravenous injection of UCNs conjugated with a tumor-targeting agent into tumor-bearing mice. As the first demonstration, to the best of our knowledge, of the photosensitizer-loaded UCN as an in vivo-targeted PDT agent, this finding may serve as a platform for future noninvasive deep-cancer therapy.
Fluorescent labels have been widely used for biological applications, primarily in imaging and assays. Traditional fluorophores such as fluorescent dyes are mainly based on downconversion fluorescence, which have several drawbacks such as photobleaching, high background noise from autofluorescence, and considerable photodamage to biological materials. Upconverting fluorescent nanoparticles emit detectable photons of higher energy in the near-infrared (NIR) or visible range upon irradiation with an NIR light in a process termed 'upconversion.' They overcome some of the disadvantages faced by conventional downconversion labels, thus making them an ideal fluorescent label for biological applications. This review looks at the development of these particles, critically examines the reported applications, and discusses their future in biomedicine.
NaYF(4):Yb,Er@SiO(2)@Ag core-shell nanocomposites were prepared to investigate metal-enhanced upconversion luminescence. Two sizes (15 and 30 nm) of Ag nanoparticles were used. The emission intensity of the upconversion nanocrystals was found to be strongly modulated by the presence of Ag nanoparticles (NPs) on the outer shell layer of the nanocomposites. The extent of modulation depended on the separation distance between Ag NPs and upconversion nanocrystals. The optimum upconversion luminescence enhancement was observed at a separation distance of 10 nm for Ag NPs with two different sizes (15 and 30 nm). A maximum upconversion luminescence enhancement of 14.4-fold was observed when 15 nm Ag nanoparticles were used and 10.8-fold was observed when 30 nm Ag NPs were used. The separation distance dependent emission intensity is ascribed to the competition between energy transfer and enhanced radiative decay rates. The biocompatibility of the nanocomposites was significantly improved by surface modification with DNA. The biological imaging capabilities of these nanocomposites were demonstrated using B16F0 cells.
The diagnosis and treatment of cancer have been greatly improved with the recent developments in nanotechnology. One of the promising nanoscale tools for cancer diagnosis is fluorescent nanoparticles (NPs), such as organic dye-doped NPs, quantum dots and upconversion NPs that enable highly sensitive optical imaging of cancer at cellular and animal level. Furthermore, the emerging development of novel multi-functional NPs, which can be conjugated with several functional molecules simultaneously including targeting moieties, therapeutic agents and imaging probes, provides new potentials for clinical therapies and diagnostics and undoubtedly will play a critical role in cancer therapy. In this article, we review the types and characteristics of fluorescent NPs, in vitro and in vivo imaging of cancer using fluorescent NPs and multi-functional NPs for imaging-guided cancer therapy.
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.
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