Browsing by Author "Young, Joseph K."
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Item Changes in Optical Properties of Plasmonic Nanoparticles in Cellular Environments are Modulated by Nanoparticle PEGylation and Serum Conditions(Springer, 2016) Chen, Allen L.; Jackson, Meredith A.; Lin, Adam Y.; Figueroa, Elizabeth R.; Hu, Ying S.; Evans, Emily R.; Asthana, Vishwaratn; Young, Joseph K.; Drezek, Rebekah A.When plasmonic nanoparticles (NPs) are internalized by cells and agglomerate within intracellular vesicles, their optical spectra can shift and broaden as a result of plasmonic coupling of NPs in close proximity to one another. For such optical changes to be accounted for in the design of plasmonic NPs for light-based biomedical applications, quantitative design relationships between designable factors and spectral shifts need to be established. Here we begin building such a framework by investigating how functionalization of gold NPs (AuNPs) with biocompatible poly(ethylene) glycol (PEG), and the serum conditions in which the NPs are introduced to cells impact the optical changes exhibited by NPs in a cellular context. Utilizing darkfield hyperspectral imaging, we find that PEGylation decreases the spectral shifting and spectral broadening experienced by 100 nm AuNPs following uptake by Sk-Br-3 cells, but up to a 33 ± 12 nm shift in the spectral peak wavelength can still occur. The serum protein-containing biological medium also modulates the spectral changes experienced by cell-exposed NPs through the formation of a protein corona on the surface of NPs that mediates NP interactions with cells: PEGylated AuNPs exposed to cells in serum-free conditions experience greater spectral shifts than in serum-containing environments. Moreover, increased concentrations of serum (10, 25, or 50 %) result in the formation of smaller intracellular NP clusters and correspondingly reduced spectral shifts after 5 and 10 h NP-cell exposure. However, after 24 h, NP cluster size and spectral shifts are comparable and become independent of serum concentration. By elucidating the impact of PEGylation and serum concentration on the spectral changes experienced by plasmonic NPs in cells, this study provides a foundation for the optical engineering of plasmonic NPs for use in biomedical environments.Item Elimination of Metastatic Melanoma Using Gold Nanoshell-Enabled Photothermal Therapy and Adoptive T Cell Transfer(Public Library of Science, 2013) Bear, Adham S.; Kennedy, Laura C.; Young, Joseph K.; Perna, Serena K.; Almeida, Joao Paulo Mattos; Lin, Adam Y.; Eckels, Phillip C.; Drezek, Rebekah A.; Foster, Aaron E.Ablative treatments such as photothermal therapy (PTT) are attractive anticancer strategies because they debulk accessible tumor sites while simultaneously priming antitumor immune responses. However, the immune response following thermal ablation is often insufficient to treat metastatic disease. Here we demonstrate that PTT induces the expression of proinflammatory cytokines and chemokines and promotes the maturation of dendritic cells within tumor-draining lymph nodes, thereby priming antitumor T cell responses. Unexpectedly, however, these immunomodulatory effects were not beneficial to overall antitumor immunity. We found that PTT promoted the infiltration of secondary tumor sites by CD11b+Ly-6G/C+ myeloid-derived suppressor cells, consequently failing to slow the growth of poorly immunogenic B16-F10 tumors and enhancing the growth of distant lung metastases. To exploit the beneficial effects of PTT activity against local tumors and on antitumor immunity whilst avoiding the adverse consequences, we adoptively transferred gp100-specific pmel T cells following PTT. The combination of local control by PTT and systemic antitumor immune reactivity provided by adoptively transferred T cells prevented primary tumor recurrence post-ablation, inhibited tumor growth at distant sites, and abrogated the outgrowth of lung metastases. Hence, the combination of PTT and systemic immunotherapy prevented the adverse effects of PTT on metastatic tumor growth and optimized overall tumor control.Item Quantifying spectral changes experienced by plasmonic nanoparticles in a cellular environment to inform biomedical nanoparticle design(Springer, 2014) Chen, Allen L.; Hu, Ying S.; Jackson, Meredith A.; Lin, Adam Y.; Young, Joseph K.; Langsner, Robert J.; Drezek, Rebekah A.Metal nanoparticles (NPs) scatter and absorb light in precise, designable ways, making them agile candidates for a variety of biomedical applications. When NPs are introduced to a physiological environment and interact with cells, their physicochemical properties can change as proteins adsorb on their surface and they agglomerate within intracellular endosomal vesicles. Since the plasmonic properties of metal NPs are dependent on their geometry and local environment, these physicochemical changes may alter the NPs' plasmonic properties, on which applications such as plasmonic photothermal therapy and photonic gene circuits are based. Here we systematically study and quantify how metal NPs' optical spectra change upon introduction to a cellular environment in which NPs agglomerate within endosomal vesicles. Using darkfield hyperspectral imaging, we measure changes in the peak wavelength, broadening, and distribution of 100-nm spherical gold NPs' optical spectra following introduction to human breast adenocarcinoma Sk-Br-3 cells as a function of NP exposure dose and time. On a cellular level, spectra shift up to 78.6 ± 23.5 nm after 24 h of NP exposure. Importantly, spectra broaden with time, achieving a spectral width of 105.9 ± 11.7 nm at 95% of the spectrum's maximum intensity after 24 h. On an individual intracellular NP cluster (NPC) level, spectra also show significant shifting, broadening, and heterogeneity after 24 h. Cellular transmission electron microscopy (TEM) and electromagnetic simulations of NPCs support the trends in spectral changes we measured. These quantitative data can help guide the design of metal NPs introduced to cellular environments in plasmonic NP-mediated biomedical technologies.Item Synthesis of a quantum nanocrystal–gold nanoshell complex for near-infrared generated fluorescence and photothermal decay of luminescence(Royal Society of Chemistry, 2014) Lin, Adam Y.; Young, Joseph K.; Nixon, Ariel V.; Drezek, Rebekah A.Multifunction nanoparticle complexes have previously been developed to aid physicians in both diagnosis and treatment of cancerous tissue. Here, we designed a nanoparticle complex structure that consists of a plasmonically active hollow gold nanoshell core surrounded by photoluminescent quantum nanocrystals (QNs) in the form of PbS encapsulated by a silica layer. There are three main design variables including HGN synthesis and optical tuning, formation of the silica layer on the hollow gold nanoshell surface, and fabrication and photoluminescence tuning of PbS quantum nanocrystals. The hollow gold nanoshells were deliberately designed to function in the optical regimes that maximize tissue transmissivity (800 nm) and minimize tissue absorption (1100 nm). Secondly, several chemical ligands were tested such as (3-mercaptopropyl)trimethoxysilane and mercaptoundecanoic acid for controlled growth of the silica layer. Last, PbS QNs were synthesized and optimized with various capping agents, where the nanocrystals excited at the same wavelength were used to activate the photothermal properties of the hollow gold nanoshells. Upon irradiation of the complex with a lower power 800 nm laser, the nanocrystals luminesce at 1100 nm. At ablative temperatures the intrinsic luminescent properties of the QNs are altered and the luminescent output is significantly reduced (>70%). While this paper focuses on synthesis and optimization of the QNﾖHGN complex, in the future we believe that this novel particle complex design may have the potential to serve as a triple theranostic agent, which will aid satellite tumor localization, photothermal treatment, and ablative confirmation.