Plasmonic Gold Nanostars for Multi-Modality Sensing and Diagnostics

Gold nanostars (AuNSs) are unique systems that can provide a novel multifunctional nanoplatform for molecular sensing and diagnostics. The plasmonic absorption band of AuNSs can be tuned to the near infrared spectral range, often referred to as the “tissue optical window”, where light exhibits minimal absorption and deep penetration in tissue. AuNSs have been applied for detecting disease biomarkers and for biomedical imaging using multi-modality methods including surface-enhanced Raman scattering (SERS), two-photon photoluminescence (TPL), magnetic resonance imaging (MRI), positron emission tomography (PET), and X-ray computer tomography (CT) imaging. In this paper, we provide an overview of the recent development of plasmonic AuNSs in our laboratory for biomedical applications and highlight their potential for future translational medicine as a multifunctional nanoplatform

Effect of Aspect Ratio and Deformability on Nanoparticle Extravasation through Nanopores

We describe the fabrication of filamentous hydrogel nanoparticles using a unique soft lithography based particle molding process referred to as PRINT (Particle Replication in Non-wetting Templates). The nanoparticles possess a constant width of 80 nm, and we varied their lengths ranging from 180 nm to 5000 nm. In addition to varying the aspect ratio of the particles, the deformability of the particles was tuned by varying the cross-link density within the particle matrix. Size characteristics such as hydrodynamic diameter and persistence length of the particles were analyzed using dynamic light scattering and electron microscopy techniques, respectively, while particle deformability was assessed by atomic force microscopy. Additionally, the ability of the particles to pass through membranes containing 0.2 μm pores was assessed by means of a simple filtration technique, and particle recovery was determined using fluorescence spectroscopy. The results show that particle recovery is mostly independent of aspect ratio at all cross-linker concentrations utilized, with the exception of 96 wt% PEG diacrylate 80 × 5000 nm particles, which showed the lowest percent recovery

Subtumoral analysis of PRINT nanoparticle distribution reveals targeting variation based on cellular and particle properties

AbstractThe biological activity of nanoparticle-directed therapies critically depends on cellular targeting. We examined the subtumoral fate of Particle Replication in Non-Wetting Templates (PRINT) nanoparticles in a xenografted melanoma tumor model by multi-color flow cytometry and in vivo confocal tumor imaging. These approaches were compared with the typical method of whole-organ quantification by radiolabeling. In contrast to radioactivity based detection which demonstrated a linear dose-dependent accumulation in the organ, flow cytometry revealed that particle association with cancer cells became dose-independent with increased particle doses and that the majority of the nanoparticles in the tumor were associated with cancer cells despite a low fractional association. In vivo imaging demonstrated an inverse relationship between tumor cell association and other immune cells, likely macrophages. Finally, variation in particle size nonuniformly affected subtumoral association. This study demonstrates the importance of subtumoral targeting when assessing nanoparticle activity within tumors.From the Clinical EditorParticle Replication in Non-Wetting Templates (PRINT) technology allows the production of nanoparticles with uniform size. The authors in the study utilized PRINT-produced nanoparticles to investigate specific tumor uptake by multi-color flow cytometry and in vivo confocal tumor imaging. This approach allowed further in-depth correlation between nanoparticle properties and tumor cells and should improve future design

A hybrid polymer gel with controlled rates of cross-link rupture and self-repair

A family of hybrid polymer gels is described, in which covalent cross-links create a permanent, stiff scaffold onto which reversible metal–ligand coordinative cross-links are added. The reversible metal–ligand interactions are shown to bear mechanical stress within the hybrid gel, and relaxations in response to that applied stress are consistent with the stress-free kinetics of ligand exchange in systems that model the reversible cross-links. The stress-induced dissociation of a model metal–ligand complex is examined by a single-molecule force spectroscopy, and its mechanical response is compared with a previously studied complex. The mechanical response of the individual interactions is relevant to those found in the family of hybrid gels, and the modular platform is therefore suitable for the study of stress-induced molecular dissociations, and their subsequent repair, within a macroscopic material of fixed structure

Plasmonic Gold Nanostars for Multi-Modality Sensing and Diagnostics

Gold nanostars (AuNSs) are unique systems that can provide a novel multifunctional nanoplatform for molecular sensing and diagnostics. The plasmonic absorption band of AuNSs can be tuned to the near infrared spectral range, often referred to as the “tissue optical window”, where light exhibits minimal absorption and deep penetration in tissue. AuNSs have been applied for detecting disease biomarkers and for biomedical imaging using multi-modality methods including surface-enhanced Raman scattering (SERS), two-photon photoluminescence (TPL), magnetic resonance imaging (MRI), positron emission tomography (PET), and X-ray computer tomography (CT) imaging. In this paper, we provide an overview of the recent development of plasmonic AuNSs in our laboratory for biomedical applications and highlight their potential for future translational medicine as a multifunctional nanoplatform

Effect of Aspect Ratio and Deformability on Nanoparticle Extravasation through Nanopores

We describe the fabrication of filamentous hydrogel nanoparticles using a unique soft lithography based particle molding process referred to as PRINT (particle replication in nonwetting templates). The nanoparticles possess a constant width of 80 nm, and we varied their lengths ranging from 180 to 5000 nm. In addition to varying the aspect ratio of the particles, the deformability of the particles was tuned by varying the cross-link density within the particle matrix. Size characteristics such as hydrodynamic diameter and persistence length of the particles were analyzed using dynamic light scattering and electron microscopy techniques, respectively, while particle deformability was assessed by atomic force microscopy. Additionally, the ability of the particles to pass through membranes containing 0.2 μm pores was assessed by means of a simple filtration technique, and particle recovery was determined using fluorescence spectroscopy. The results show that particle recovery is mostly independent of aspect ratio at all cross-linker concentrations utilized, with the exception of 96 wt % PEG diacrylate 80 × 5000 nm particles, which showed the lowest percent recovery