Ryan D. Roeder

Selective Imaging and Killing of Cancer Cells with Protein-Activated Near-Infrared Fluorescing Nanoparticles

We present a general approach for the selective imaging and killing of cancer cells using protein-activated near-infrared emitting and cytotoxic oxygen generating nanoparticles. Poly(propargyl acrylate) (PA) particles were surface modified through the copper-catalyzed azide/alkyne cycloaddition of azide-terminated indocyanine green (azICG), a near-infrared emitter, and poly(ethylene glycol) (azPEG) chains of various molecular weights. The placement of azICG onto the surface of the particles allowed for the chromophores to complex with bovine serum albumin when dispersed in PBS that resulted in an enhancement of the dye emission. In addition, the inclusion of azPEG with the chromophores onto the particle surface resulted in a synergistic ninefold enhancement of the fluorescence intensity, with azPEGs of increasing molecular weight amplifying the response. Human liver carcinoma cells (HepG2) overexpress albumin proteins and could be employed to activate the fluorescence of the nanoparticles. Preliminary PDT studies with HepG2 cells combined with the modified particles indicated that a minor exposure of 780 nm radiation resulted in a statistically significant reduction in cell growth.

Colloidal templating: seeded emulsion polymerization of a soluble shell with a controlled alkyne surface density

A general methodology for producing ca. 100 nm core–shell colloidal particles in which the shell has an elevated alkyne functionality and yet remains thermoplastic is presented. The availability of accessible alkyne groups on the surface of the aqueous-phase particles allows for the in situ surface modification of the particles through a copper(I) catalyzed Huisgen 1,3-dipolar cycloaddition with an azide-terminated surface agent. The core is an extensively crosslinked polymer which can be easily removed by dispersing the particles in a solvent and centrifuging and collecting the cores, leaving the solubilized shells. This allows for the complete characterization of the colloidal surface reactions in the absence of the volumetrically dominant core. The technique is demonstrated with a core–shell colloid composed of a 135 nm crosslinked polystyrene (PS) core coated with a ca. 10 nm thick uncrosslinked poly(methyl acrylate-co-propargyl acrylate) shell. Due to the applicability of this technique for generating particles useful in biomedical imaging or drug delivery applications, the core–shell particles are surface modified with a variety of azide-terminated poly(ethylene glycol) (PEG) derivatives, including a poloxamer which was terminated on either end by an azide and a naphthalimide chromophore. The resulting fluorescent particles had an absorbance at 413 nm and peak emission at 525 nm. The PEG derivatives could be attached to the particles at a grafting density of ca. 0.2–0.3 groups/nm2.

Click functionalization of thin films fabricated by roll-to-roll printing of thermoplastic/thermoset core-shell colloids

AbstractA general methodology for producing ca. 140-nm thermoplastic/thermoset, core-shell colloids that are used as an ink in roll-to-roll printing is demonstrated. The printed films are subsequently modified in-line through a dip-click approach using the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC). The thermoplastic nature of the shell polymers in the particles allows the shell to delaminate when annealed above its glass transition temperature. This results in a printed film that is more robust and functional as it combines the durability of the thermoset core colloids and the flexibility of the thermoplastic shell polymers. The technique is demonstrated using core-shell particles with a crosslinked polystyrene core and co-/terpolymer shell that contains terminal alkynes for click functionalization. The core-shell particles were roll-to-roll printed and then annealed at 100 ∘C to yield coalesced films. The printed films were dipped in a solution containing an azide-modified fluorescein dye which resulted in the covalent attachment of the dye to the thin films via CuAAC. When the click reaction was allowed to proceed for 24 h, it was found that ca. 67% of the total functionalization occurred in the first hour. Due to the efficiency of this technique, the potential for large-scale production of printed films where an in-line chemical modification via CuAAC could be realized. Graphical AbstractA general methodology for producing ca. 140 nm thermoplastic/thermoset, core-shell colloids that can be used as an ink in roll-to-roll printing is demonstrated. The printed films are subsequently modified inline through a dip-click approach using the copper(I)- catalyzed azide-alkyne cycloaddition (CuAAC). The thermoplastic nature of the shell polymers in the particles allows the shell to delaminate when annealed above its glass transition temperature. This results in a printed film that is more robust and functional as it combines the durability of a thermoset core colloid with the flexibility of an alkyne-functionalized thermoplastic shell.