Folate receptor targeting silica nanoparticle probe for two-photon fluorescence bioimaging
Spotlight summary: The development of nanoparticles for imaging and therapeutic applications is actively being researched. Promising applications such as disease-targeted drug delivery, release of cytotoxic drugs over time for improved therapeutic efficacy, and high-contrast imaging are currently under investigation. Inorganic nanoparticles of a variety of materials have been studied, whereas common inorganic materials for nanoparticle synthesis are gold, titanium dioxide, and silica. Although many promising applications for nanoparticles have been investigated in preclinical models, the most significant drawback to their use is long-term toxicity following systemic administration. To date, gold nanoparticles have shown dose-dependent toxicity in mice, while the toxicity of titanium dioxide particles depends on their phase composition, and colloidal silica has been shown to be relatively nontoxic in rats. As with other imaging and therapeutic molecules, nanoparticles must be appropriately targeted to the cells of interest. For cancer imaging and therapy, folate-targeted agents have shown promising results in preclinical as well as clinical studies. About 40% of all human cancers overexpress the alpha isoform of the folate receptor. Some cancers such as ovarian and brain cancers show homogeneous upregulation of this receptor with up to 90% of cancers overexpressing the folate receptor. Other solid tumors, such as those found in breast and head/neck cancers, have more variable folate receptor expression with only about 50% showing overexpression. Clinical trials of folate-receptor-targeted drugs have shown promising results with decreased tumor burden and minimal toxicity.
In the work published here by Wang et al., silica nanoparticles entrapping a hydrophobic two-photon absorbing fluorenyl dye were synthesized. The surface of the silica nanoparticles was treated with folic acid to specifically deliver the nanoparticles to cells with overexpression of the folate receptor. Encapsulation of the hydrophobic fluorenyl dye in the silica nanoparticles yielded significantly better photostability than the free dye in organic solvent—an important property for two-photon microscopy. The silica nanoparticles were found to be nontoxic to cells at concentrations useful for cellular microscopy. The specificity of the folic acid–treated nanoparticles was confirmed via fluorescence microscopy of cells with high and low folate receptor expression. Significantly, more fluorescence signal was seen in the high folate receptor expression cells; this signal could be blocked by treating the cells with folic acid prior to incubation with the nanoparticles. The folate-modified, dye-containing silica nanoparticles are efficient probes for two-photon as well as fluorescence lifetime microscopy. Future studies on folate receptor status of patient specimens could lead to useful applications.
ToC Category: Nanotechnology and Plasmonics
|OCIS Codes:||(170.0170) Medical optics and biotechnology : Medical optics and biotechnology|
|(170.2520) Medical optics and biotechnology : Fluorescence microscopy|
|(170.3880) Medical optics and biotechnology : Medical and biological imaging|
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