Highly Robust, Recyclable Displacement Assay for Mercuric Ions in Aqueous Solutions and Living Cells

We designed a recyclable Hg²⁺ probe based on Rhodamine B isothiocyanate (RBITC)-poly(ethylene glycol) (PEG)-comodified gold nanoparticles (AuNPs) with excellent robustness, selectivity, and sensitivity. On the basis of a rational design, only Hg²⁺ can displace RBITC from the AuNP surfaces, resulting in a remarkable enhancement of RBITC fluorescence initially quenched by AuNPs. To maintain stability and monodispersity of AuNPs in real samples, thiol-terminated PEG was employed to bind with the remaining active sites of AuNPs. Besides, this displacement assay can be regenerated by resupplying free RBITC into the AuNPs solutions that were already used for detecting Hg²⁺. Importantly, the detection limit of this assay for Hg²⁺ (2.3 nM) was lower than the maximum limits guided by the United States Environmental Protection Agency as well as that permitted by the World Health Organization. The efficiency of this probe was demonstrated in monitoring Hg²⁺ in complex samples such as river water and living cells

Self-Assembly of Amphiphilic Plasmonic Micelle-Like Nanoparticles in Selective Solvents

Amphiphilic plasmonic micelle-like nanoparticles (APMNs) composed of gold nanoparticles (AuNPs) and amphiphilic block copolymers (BCPs) structurally resemble polymer micelles with well-defined architectures and chemistry. The APMNs can be potentially considered as a prototype for modeling a higher-level self-assembly of micelles. The understanding of such secondary self-assembly is of particular importance for the bottom-up design of new hierarchical nanostructures. This article describes the self-assembly, modeling, and applications of APMN assemblies in selective solvents. In a mixture of water/tetrahydrofuran, APMNs assembled into various superstructures, including unimolecular micelles, clusters with controlled number of APMNs, and vesicles, depending on the lengths of polymer tethers and the sizes of AuNP cores. The delicate interplay of entropy and enthalpy contributions to the overall free energy associated with the assembly process, which is strongly dependent on the spherical architecture of APMNs, yields an assembly diagram that is different from the assembly of linear BCPs. Our experimental and computational studies suggested that the morphologies of assemblies were largely determined by the deformability of the effective nanoparticles (that is, nanoparticles together with tethered chains as a whole). The assemblies of APMNs resulted in strong absorption in near-infrared range due to the remarkable plasmonic coupling of Au cores, thus facilitating their biomedical applications in bioimaging and photothermal therapy of cancer

Gold Nanoparticle-Based Activatable Probe for Sensing Ultralow Levels of Prostate-Specific Antigen

It is still in high demand to develop extremely sensitive and accurate clinical tools for biomarkers of interest for early diagnosis and monitoring of diseases. In this report, we present a highly sensitive and compatible gold nanoparticle (AuNP)-based fluorescence-activatable probe for sensing ultralow levels of prostate-specific antigen (PSA) in patient serum samples. The limit of detection of the newly developed probe for PSA was pushed down to 0.032 pg/mL, which is more than 2 orders of magnitude lower than that of the conventional fluorescence probe. The ultrahigh sensitivity of this probe was attributed to the high loading efficiency of the dyes on AuNP surfaces and high fluorescence quenching–unquenching abilities of the dye–AuNP pairs. The efficiency and robustness of this probe were investigated in patient serum samples, demonstrating the great potential of this probe in real-world applications

Self-Illuminating ⁶⁴Cu-Doped CdSe/ZnS Nanocrystals for in Vivo Tumor Imaging

Construction of self-illuminating semiconducting nanocrystals, also called quantum dots (QDs), has attracted much attention recently due to their potential as highly sensitive optical probes for biological imaging applications. Here we prepared a self-illuminating QD system by doping positron-emitting radionuclide ⁶⁴Cu into CdSe/ZnS core/shell QDs via a cation-exchange reaction. The ⁶⁴Cu-doped CdSe/ZnS QDs exhibit efficient Cerenkov resonance energy transfer (CRET). The signal of ⁶⁴Cu can accurately reflect the biodistribution of the QDs during circulation with no dissociation of ⁶⁴Cu from the nanoparticles. We also explored this system for in vivo tumor imaging. This nanoprobe showed high tumor-targeting ability in a U87MG glioblastoma xenograft model (12.7% ID/g at 17 h time point) and feasibility for in vivo luminescence imaging of tumor in the absence of excitation light. The availability of these self-illuminating integrated QDs provides an accurate and convenient tool for in vivo tumor imaging and detection

Design Considerations of Iron-Based Nanoclusters for Noninvasive Tracking of Mesenchymal Stem Cell Homing

Stem-cell-based therapies have attracted considerable interest in regenerative medicine and oncological research. However, a major limitation of systemic delivery of stem cells is the low homing efficiency to the target site. Here, we report a serendipitous finding that various iron-based magnetic nanoparticles (MNPs) actively augment chemokine receptor CXCR4 expression of bone-marrow-derived mesenchymal stem cells (MSCs). On the basis of this observation, we designed an iron-based nanocluster that can effectively label MSCs, improve cell homing efficiency, and track the fate of the cells <i>in vivo</i>. Using this nanocluster, the labeled MSCs were accurately monitored by magnetic resonance imaging and improved the homing to both traumatic brain injury and glioblastoma models as compared to unlabeled MSCs. Our findings provide a simple and safe method for imaging and targeted delivery of stem cells and extend the potential applications of iron-based MNPs in regenerative medicine and oncology

A Facile, One-Step Nanocarbon Functionalization for Biomedical Applications

Despite their immense potential in biomedicine, carbon nanomaterials suffer from inefficient dispersion and biological activity in vivo. Here we utilize a single, yet multifunctional, hyaluronic acid-based biosurfactant to simultaneously disperse nanocarbons and target single-walled carbon nanotubes (SWCNTs) to CD44 receptor positive tumor cells with prompt uptake. Cellular uptake was monitored by intracellular enzyme-activated fluorescence, and localization of SWCNTs within cells was further confirmed by Raman mapping. In vivo photoacoustic, fluorescence, and positron emission tomography imaging of coated SWCNTs display high tumor targeting capability while providing long-term, fluorescence molecular imaging of targeted enzyme events. By utilizing a single biomaterial surfactant for SWCNT dispersion without additional bioconjugation, we designed a facile technique that brings nanocarbons closer to their biomedical potential

Chelator-Free ⁶⁴Cu-Integrated Gold Nanomaterials for Positron Emission Tomography Imaging Guided Photothermal Cancer Therapy

Using positron emission tomography (PET) imaging to monitor and quantitatively analyze the delivery and localization of Au nanomaterials (NMs), a widely used photothermal agent, is essential to optimize therapeutic protocols to achieve individualized medicine and avoid side effects. Coupling radiometals to Au NMs <i>via</i> a chelator faces the challenges of possible detachment of the radiometals as well as surface property changes of the NMs. In this study, we reported a simple and general chelator-free ⁶⁴Cu radiolabeling method by chemically reducing ⁶⁴Cu on the surface of polyethylene glycol (PEG)-stabilized Au NMs regardless of their shape and size. Our ⁶⁴Cu-integrated NMs are proved to be radiochemically stable and can provide an accurate and sensitive localization of NMs through noninvasive PET imaging. We further integrated ⁶⁴Cu onto arginine-glycine-aspartic acid (RGD) peptide modified Au nanorods (NRs) for tumor theranostic application. These NRs showed high tumor targeting ability in a U87MG glioblastoma xenograft model and were successfully used for PET image-guided photothermal therapy

Effect of Injection Routes on the Biodistribution, Clearance, and Tumor Uptake of Carbon Dots

The emergence of photoluminescent carbon-based nanomaterials has shown exciting potential in the development of benign nanoprobes. However, the <i>in vivo</i> kinetic behaviors of these particles that are necessary for clinical translation are poorly understood to date. In this study, fluorescent carbon dots (C-dots) were synthesized and the effect of three injection routes on their fate <i>in vivo</i> was explored by using both near-infrared fluorescence and positron emission tomography imaging techniques. We found that C-dots are efficiently and rapidly excreted from the body after all three injection routes. The clearance rate of C-dots is ranked as intravenous > intramuscular > subcutaneous. The particles had relatively low retention in the reticuloendothelial system and showed high tumor-to-background contrast. Furthermore, different injection routes also resulted in different blood clearance patterns and tumor uptakes of C-dots. These results satisfy the need for clinical translation and should promote efforts to further investigate the possibility of using carbon-based nanoprobes in a clinical setting. More broadly, we provide a testing blueprint for <i>in vivo</i> behavior of nanoplatforms under various injection routes, an important step forward toward safety and efficacy analysis of nanoparticles