Elongated nanoparticles have recently been shown to have distinct advantages over their spherical counterparts in drug delivery applications. Cellulose nanocrystals (CNCs) have rodlike shapes in nature and have demonstrated biocompatibility in a variety of mammalian cell lines. In this report, CNCs are put forward as a modular platform for the production of multifunctional rod-shaped nanoparticles for cancer imaging and therapy. For the first time, PEGylated metal-chelating polymers containing diethylenetriaminepentaacetic acid (DTPA) (i.e., mPEG-PGlu(DPTA)18-HyNic and PEG-PGlu(DPTA)25-HyNic) are conjugated to CNCs to enable the chelation of radionuclides for diagnostic and therapeutic applications. The entire conjugation is based on UV/vis-quantifiable bis-aryl hydrazone-bond formation, which allows direct quantification of the polymers grafted onto the CNCs. Moreover, it has been shown that the mean number of polymers grafted per CNC could be controlled. The CNCs are also fluorescently labeled with rhodamine and Alexa Fluor 488 by embedding the probes in the polymer corona. Preliminary evaluation in a human ovarian cancer cell line (HEYA8) demonstrated that these CNCs are nontoxic and their penetration properties can be readily assessed in multicellular tumor spheroids (MCTSs) by optical imaging. These findings provide support for biomedical applications of CNCs, and further in vitro and in vivo studies are warranted to evaluate their potential as imaging and therapeutic agents for cancer treatment.

A size- and shape-selective synthesis of pentagonally twinned silver icosahedral nanoparticles (AgIhNPs), one of the five platonic solid morphologies, has been developed by integrating three key factors: nuclei templating by copper, photochemical development using violet LED light and chemical oxidative etching. The presence of copper is essential for AgIhNP shape selection via the promotion of icosahedral nuclei in precursor NPs. Violet light (401-410 nm) is crucial to promote plasmonic selection of near-spherical AgIhNPs. Oxidative etching with hydrogen peroxide and photochemical reduction with citrate establishes a red-ox equilibrium for the photochemical selection of AgIhNPs. The addition of chloride ions improves size- and shape-selectivity. Finally, the demonstration of 1-D growth of AgIhNPs to pentagonal pins initiated at AgIhNP pentagonal-twinned defects highlights a universal role of twinned defects for the formation of anisotropic nanoparticles.

Ligand-free stellated gold nanoparticles (AuStNPs) with well-defined octahedral (O(h)) and icosahedral (I(h)) core symmetries were prepared using hydrogen peroxide as a reducing agent. Only three reagents: gold precursor (HAuCl4), H2O2 and NaOH were required to form colloidally and chemically stable AuStNPs with a zeta-potential between -55 and -40 mV indicative of excellent charge stabilization. The size and degree of stellation of AuStNPs can be controlled by several synthetic parameters so that the localized surface plasmon resonance (LSPR) can be varied from ca. 850 nm in near-infrared (NIR) to ca. 530 nm. In particular, AuStNP size and LSPR tuning can be conveniently accomplished by iodide variation. The size distribution of AuStNPs was improved by nucleation with ascorbic acid, and the AuStNP size and degree of branching could be readily modified using arginine. AuStNPs are advantageous for SPR sensing, as it was demonstrated in the sensitive detection of not only thiols, such as ampicillin, but also iodide with the detection limit of 3.2 pM (0.4 ng L(-1)). The reported ligand-free stable AuStNPs thus should be very useful for biodiagnostics based on SPR sensing and potentially for SERS and hyperthermia therapy.

We are interested in developing lanthanide nanoparticles (LnNPs) of the general formula NaLnF 4 as high-sensitivity reagents for mass cytometry. These LnNPs must be coated to provide colloidal stability in aqueous buffer and functionality for detecting cellular biomarkers. Lipid bilayer coatings are a promising approach, but one requires an analytical technique to enable characterization of the NP coating composition as opposed to the composition of the lipid formulation used in the coating process. However, quantification of the lipid composition of lipid coatings on polymer and inorganic NPs is not common practice in the field.Here we describe a method based on high-performance liquid chromatography (LC) for separations and triple quadrupole tandem mass spectrometry (MS/MS) instrumentation for detection and show that it can quantify complex lipid mixtures using small (<1 μg) amounts of sample. Our lipid formulation consisted of a mixture of egg sphingomyelin, 1,2-dioleoyl-sn-glycero-3-phosphocholine, 1,2-dioleoyl-3-trimethylammonium-propane, cholesterol-PEG600, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[biotinyl(polyethylene glycol)-2000]. We were able to extract the coating from lipid-coated 35 nm diameter LnNPs, quantify the lipid/NP ratio, and show that the coating composition differed from the composition of the lipid formulation for several of the species. Knowledge of the actual composition of the lipid coating for lipidcoated NPs is critical for designing and optimizing application of these materials. Our results establish the value of LC-MS/MS characterization of lipid-coated NPs, thus providing an important new addition to the toolbox available for characterizing these types of nanomaterials.

Elongated colloidal nanoparticles (NPs) have significant potential for drug delivery and imaging applications in cancer therapy, but progress depends on developing a deeper understanding of how their physicochemical properties affect their interactions with cells and with tumors. Cellulose nanocrystals (CNCs) are biocompatible, rodlike colloids that are broadly surface-functionalizable, making them interesting as modular drug carriers. In this report, we describe the attachment of a statistical copolymer containing oligoethylene glycol methacrylate (OEGMA; M n ≈ 500 Da) and small amounts of aminopropylmethacrylamide (APMA) to CNCs. Here, the copolymer is designed to serve as a "stealth" corona to minimize protein adsorption, and the amino groups provide functionality for the attachment of diagnostic or therapeutic moieties. The corona polymer with a terminal azide group was synthesized by atom transfer radical polymerization using tertbutyloxycarbonyl (tBoc)-protected APMA as the comonomer. A key step in this synthesis was the grafting of acetylene groups to the CNC surface via a reaction with NaOH plus propargyl bromide in aqueous dimethyl sulfoxide. The copolymer was attached to the CNCs using copper-catalyzed azide−alkyne cycloaddition (CuAAC) "click" chemistry. By determining the mean number of amino groups per copolymer and amino group content of the CNC sample, we were able to infer that there were on average ca. 300 polymer molecules per CNC. Preliminary evaluation in a human ovarian cancer cell line (HEYA8) and a human breast cancer cell line (MDA-MB-436) demonstrated that these CNCs are nontoxic. We also assessed the cellular uptake of these CNC NPs in the same two cell lines using flow cytometry and distinguished between NPs being internalized by the cell or surface-bound using a trypan blue quenching experiment. These results provide support for applications of polymer-coated CNCs in medicine and are encouraging for further studies in vitro and in vivo to evaluate their potential as drug-delivery vehicles.