The development and applications of ultrabright mesoporous silica nanoparticles.
Peerzade, Saquib Ahmed.
2020
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Thesis
(Ph.D.)--Tufts University, 2020.
Submitted to the Dept. of Biomedical Engineering.
Advisor: Igor Sokolov.
Committee: Fiorenzo Omenetto, Mark Cronin-Golomb, Hyunmin Yi, and Hui Feng.
Keywords: Biomedical engineering, Nanoscience, and Nanotechnology.
Nanoparticles that can target, detect, and eliminate cancerous cells, multiplex, sense pH ... read moreand temperature are of wide interest in medicine, flow cytometry, anti-counterfeiting, and fundamental understanding of cellular functions. Ultrabright fluorescent mesoporous silica particles provide a promising platform for the development of highly fluorescent agents and novel optical sensors to study various diseases, in particular, cancer. Ultrabright fluorescent nanoparticles exhibit several advantages such as faster tumor detection capabilities, high contrast or signal-to-noise ratio with a low number of particles, imaging along with demultiplexing and sensing down to the nanoscale level, low cytotoxicity, and low phototoxicity. Herein, two major applications of ultrabright fluorescent nanoparticles are demonstrated, namely tumor targeting in-vivo, and pH and temperature dual-sensing and also investigated multiplexing. For tumor targeting in-vivo, a zebrafish model was used. Three designs of conjugating ultrabright nanoparticles with polyethylene glycol (PEG) and folate groups were studied. To demonstrate the advantages of ultrabrightness, we repeated the experiments with similar but 200× less bright particles (the brightness similar to the one of quantum dots). Compared to those, ultrabright particles showed ∼3× faster tumor detection and ∼2× higher relative fluorescent contrast of tumors/cancer cells. For multiplexing, we report on a first demonstration of the synthesis of ultrabright fluorescent silica nanoparticles (Star-dots), which have a large number of complex fluorescence spectra suitable for studying multiplexing. We demonstrate that the mixture of ~100 particles with two different spectra can be distinguished by using a linear decomposition method with a rather high precision of 12% error within 0.5 seconds. For simultaneous acidity (pH) and temperature measurements, FRET pairs of the temperature-responsive, pH sensing, and reference dyes were physically encapsulated inside a porous silica matrix of 40 nm particles. We demonstrate that the particles can be used to measure both the temperature in 25 to 45˚C and pH in 4 to 7 range with a mean absolute deviation of less than 1˚C and 0.1, respectively.read less - ID:
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