The mean square displacement ⟨r⟩ of nanoparticle probes dispersed in simple isotropic liquids and in polymer solutions is interrogated using fluorescence correlation spectroscopy and single-particle tracking (SPT) experiments. Probe dynamics in different regimes of particle diameter (d), relative to characteristic polymer length scales, including the correlation length (ξ), the entanglement mesh size (a), and the radius of gyration (R), are investigated. In simple fluids and for polymer solutions in which d ≫ R, long-time particle dynamics obey random-walk statistics ⟨r⟩:t, with the bulk zero-shear viscosity of the polymer solution determining the frictional resistance to particle motion. In contrast, in polymer solutions with d < R, polymer molecules in solution exert noncontinuum resistances to particle motion and nanoparticle probes appear to interact hydrodynamically only with a local fluid medium with effective drag comparable to that of a solution of polymer chain segments with sizes similar to those of the nanoparticle probes. Under these conditions, the nanoparticles exhibit orders of magnitude faster dynamics than those expected from continuum predictions based on the Stokes-Einstein relation. SPT measurements further show that when d > a, nanoparticle dynamics transition from diffusive to subdiffusive on long timescales, reminiscent of particle transport in a field with obstructions. This last finding is in stark contrast to the nanoparticle dynamics observed in entangled polymer melts, where X-ray photon correlation spectroscopy measurements reveal faster but hyperdiffusive dynamics. We analyze these results with the help of the hopping model for particle dynamics in polymers proposed by Cai et al. and, on that basis, discuss the physical origins of the local drag experienced by the nanoparticles in entangled polymer solutions.

In contrast to small molar mass compounds, detailed structural investigations of inorganic coreorganic ligand shell hybrid nanoparticles remain challenging. Assessment of batch reaction induced heterogeneities of surface chemical properties and their correlation with particle size has been a particularly long-standing issue. Applying a combination of high performance liquid chromatography (HPLC) and gel permeation chromatography (GPC) to ultrasmall (< 10 nm diameter) poly(ethylene glycol) coated (PEGylated) fluorescent core-shell silica nanoparticles, here we elucidate previously unknown surface heterogeneities resulting from varying dye conjugation to nanoparticle silica cores and surfaces. Heterogeneities are predominantly governed by dye charge as corroborated by molecular dynamics simulations. We demonstrate that this insight enables development of synthesis protocols to achieve PEGylated and targeting ligand functionalized PEGylated silica nanoparticles with dramatically improved surface chemical homogeneity as evidenced by single peak HPLC chromatograms. Since surface chemical properties are key to all nanoparticle interactions, we expect these methods and fundamental insights to become relevant to a number of systems for applications including bioimaging and nanomedicine.

Synthetic advances in the formation of ultrasmall (<10 nm) fluorescent poly(ethylene glycol)-coated (PEGylated) core-shell silica nanoparticles (SNPs), enabling improved particle size and surface chemical property control have led to successful clinical translation of SNPs as diagnostic probes in oncology. Despite the success of such probes, details of the dye incorporation and resulting silica architecture are still poorly understood. Here, we employ afterpulse-corrected fluorescence correlation spectroscopy (FCS) to monitor fast fluorescence fluctuations (lag times <10−5 s) of the negatively charged cyanine dye Cy5 as a probe to study such details for dye encapsulation in 5 nm silica cores of PEGylated core-shell SNPs (C dots). Upon deposition of additional silica shells over the silica core we find that the amplitude of photo-induced cis-trans isomerization decreases, suggesting that the Cy5 dyes are located near or on the surface of the original SNP cores. In combination with time correlated fluorescence decay measurements we deduce radiative and non-radiative rates of the Cy5 dye in these particles. Results demonstrate that FCS is a well-suited tool to investigate aspects of the photophysics of fluorescent nanoparticles, and that conformational changes of cyanine dyes like Cy5 are excellent indicators for the local dye environment within ultrasmall SNPs.

In quantum materials macroscopic behavior is governed in non-trivial ways by quantum phenomena. This is usually achieved by exquisite control over atomic positions in crystalline solids. Here we demonstrate that the use of disordered glassy materials provides unique opportunities to tailor quantum material properties. By borrowing ideas from single molecule spectroscopy, we isolate single delocalized π-electron dye systems in relatively rigid ultrasmall (<10nm diameter) amorphous silica nanoparticles. We demonstrate that chemically tuning the local amorphous silica environment around the dye over a range of compositions enables exquisite control over dye quantum behavior, leading to efficient probes for photodynamic therapy (PDT) and stochastic optical reconstruction microscopy (STORM). Results suggest that efficient fine-tuning of light-induced quantum behavior mediated via effects like spin-orbit coupling can be effectively achieved by systematically varying averaged local environments in glassy amorphous materials as opposed to tailoring well-defined neighboring atomic lattice positions in crystalline solids. Resulting nanoprobes have required features proven to enable clinical translation.

Photodynamic therapy (PDT) presents an alternative noninvasive therapeutic modality for the treatment of cancer and other diseases. PDT relies on cytotoxic singlet oxygen (reactive oxygen species or ROS) that is locally generated through energy transfer between a photosensitizer (PS) and molecularly dissolved triplet oxygen. While a number of nanoparticle-based PS vehicles have been described, because of their beneficial and proven biodistribution and pharmacokinetic profiles, ultrasmall nanoparticles with diameters below 10 nm are particularly promising. Here, we investigate two different particle designs deviating from ultrasmall poly­(ethylene glycol)-coated (PEGylated) fluorescent core–shell silica nanoparticles referred to as Cornell prime dots (C′ dots) by replacing the fluorescent dye with a photosensitizer (psC′ dots), here the methylene blue (MB) derivate MB2. In the first approach (design 1), MB2 is encapsulated into the matrix of the silica core, while in the second approach (design 2), MB2 is grafted onto the silica core surface in between chains of the sterically stabilizing poly­(ethylene glycol) (PEG) corona. We compare both cases with regard to their singlet oxygen quantum yields, ΦΔ, with the effective ΦΔ eff per particle reaching 111 ± 3 and 161 ± 5% for designs 1 and 2, respectively, substantially exceeding single MB2 molecule performance. Encapsulation significantly improves PS photostability, while surface conjugation diminishes it, relative to free MB2. Finally, we show that both particle designs allow functionalization with a targeting peptide, cyclo­(Arg-Gly-Asp-D-Tyr-Cys) [c­(RGDyC)]. Results suggest that psC′ dots are a promising targeted platform for PDT applications, e.g. in oncology, that may combine colloidal stability, efficient renal clearance limiting off-target accumulation, targeted delivery to sites of disease, and effective ROS generation maximizing therapeutic efficacy.