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Targeted drug delivery using functional nanoparticles has provided new strategies for improving therapeutic efficacy while concurrently minimizing toxicity. Photodynamic therapy is an approach that offers control of drug delivery by use of an external photon source to allow active therapeutic release to a target area. Upconverting nanoparticles (UCNPs) have potential to operate as integral components of photodynamic therapeutic platforms based on the resonant absorption of near-infrared (NIR) radiation and emission at shorter wavelengths. NIR radiation is minimally absorbed and scattered by biological tissues, and the NIR excitation of UCNPs can generate anti-Stokes emission in the ultraviolet-visible wavelength range at intensities that can be used to trigger cleavage of bonds linking therapeutics at the nanoparticle interface. Herein, we describe an investigation of photocleavage at the surface of UCNPs to release the chemotherapeutic 5-fluorouracil (5-FU). Core-shell UCNPs composed of a β-NaYF4: 4.95% Yb, 0.08% Tm core and a β-NaYF4 shell were coated with o-phosphorylethanolamine ligands and coupled to an o-nitrobenzyl (ONB) derivative of 5-FU. NIR excitation of the UCNPs resulted in photoluminescence (PL) emission bands centered at 365, 455, and 485 nm. The UV-blue PL was in resonance with the absorption band of the ONB-FU derivative resulting in photocleavage and subsequent release of the 5-FU drug from the UCNPs for these in vitro studies. The release of 5-FU was complete in <14 min using a NIR laser source centered at 980 nm that operated at a power of <100 mW. The efficiency of triggered release was as high as 77% of the total ONB-FU conjugate, while the rate of drug release could be tuned with the laser power output. This work provides an important first step in the development of a UCNP platform capable of targeted chemotherapy.

Monodisperse aqueous upconverting nanoparticles (UCNPs) were covalently immobilized on aldehyde modified cellulose paper via reduction amination to develop a luminescence resonance energy transfer (LRET)-based nucleic acid hybridization assay. This first account of covalent immobilization of UCNPs on paper for a bioassay reports an optically responsive method that is sensitive, reproducible and robust. The immobilized UCNPs were decorated with oligonucleotide probes to capture HPRT1 housekeeping gene fragments, which in turn brought reporter conjugated quantum dots (QDs) in close proximity to the UCNPs for LRET. This sandwich assay could detect unlabeled oligonucleotide target, and had a limit of detection of 13 fmol and a dynamic range spanning nearly 3 orders of magnitude. The use of QDs, which are excellent LRET acceptors, demonstrated improved sensitivity, limit of detection, dynamic range and selectivity compared to similar assays that have used molecular fluorophores as acceptors. The selectivity of the assay was attributed to the decoration of the QDs with polyethylene glycol to eliminate non-specific adsorption. The kinetics of hybridization were determined to be diffusion limited and full signal development occurred within 3 min.

As teaching laboratories stand empty in light of COVID-19, we extended the practical experience from the laboratory to the safety of the students’ homes. We developed a simple, robust, and versatile at-home experiment that teaches solution preparation, calibration curves, real-life sample preparation, and data analysis to second-year analytical chemistry students. Solutions were prepared using common kitchen tools and readily available corn starch, syringes, and trophic iodine for a low cost below $20. A calibration curve for the brightness of corn starch–iodine solutions as a function of starch concentration was prepared. Solutions were imaged using a smartphone camera, and the brightness of each solution was quantified using ImageJ. Starch was extracted from a ripe banana and quantified using the calibration curve. Extending the practical experience to students’ homes in the age of COVID-19 not only provides them with a better sense of the real chemistry laboratory they will one day return to but also helps solidify and expand on key concepts learned in the virtual classroom.

Monodisperse water-soluble upconverting nanoparticles (UCNPs) were immobilized onto modified glass substrates for development of biosensing surfaces that operated using luminescence resonance energy transfer (LRET). Amine modified UCNPs were prepared from oleic acid capped UCNPs by ligand exchange using o-phosphorylethanolamine (PEA). PEA-UCNPs were covalently immobilized on aldehyde functionalized coverslips. Environmental scanning electron microscopy (ESEM) images indicated a homogeneous distribution of UCNPs on surfaces with a high immobilization density of approximately 1.3 × 10(11) UCNP cm(-2). This is the first account of covalent immobilization of UCNPs for bioassay and biosensor development where the density is on par with the high immobilization densities reported for other types of nanoparticles. The functionality and stability of the immobilized NPs were demonstrated by examining an LRET-based bioassay. The well-known sandwich assay for the detection of thrombin was selected as a model in which UCNPs were used as donors and quantum dots (QDs) as acceptors. The closely packed UCNPs on the glass surface showed a 2.5-fold enhancement in assay sensitivity compared to less-densely packed surfaces. In addition, a 1.5-fold enhancement in energy transfer efficiency was shown for solid-phase compared to solution-phase LRET.