Physicochemical Properties and Route of Systemic Delivery Control the In Vivo Dynamics and Breakdown of Radiolabeled Gold Nanostars.

The in vivo dynamics of nanoparticles requires a mechanistic understanding of multiple factors. Here, for the first time, the surprising breakdown of functionalized gold nanostars (F-AuNSs) conjugated with antibodies and 64 Cu radiolabels in vivo and in artificial lysosomal fluid ex vivo, is shown. The short-term biodistribution of F-AuNSs is driven by the route of systemic delivery (intravenous vs intraperitoneal) and long-term fate is controlled by the tissue type in vivo. In vitro studies including endocytosis pathways, intracellular trafficking, and opsonization, are combined with in vivo studies integrating a milieu of spectroscopy and microcopy techniques that show F-AuNSs dynamics is driven by their physicochemical properties and route of delivery. F-AuNSs break down into sub-20 nm broken nanoparticles as early as 7 days postinjection. Martini coarse-grained simulations are performed to support the in vivo findings. Simulations suggest that shape, size, and charge of the broken nanoparticles, and composition of the lipid membrane depicting various tissues govern the interaction of the nanoparticles with the membrane, and the rate of translocation across the membrane to ultimately enable tissue clearance. The fundamental study addresses critical gaps in the knowledge regarding the fate of nanoparticles in vivo that remain a bottleneck in their clinical translation.

Elemental Characterization of Leaded and Lead-Free Inorganic Primer Gunshot Residue Standards Using Single Particle Inductively Coupled Plasma Time-of-Flight Mass Spectrometry.

This study describes the use of single particle inductively coupled plasma time-of-flight mass spectrometry (spICP-TOFMS) for the detection and classification of inorganic gunshot residue (IGSR) particles. To establish reliable multi-element criteria to classify IGSR particles, leaded and lead-free IGSR reference materials were analyzed, and the elemental compositions of the individual particles were quantified. The results suggest that expanded element compositions may be used to classify IGSR particles via spICP-TOFMS compared to those used in conventional IGSR analysis using scanning electron microscopy energy dispersive X-ray spectroscopy (SEM-EDS). For spICP-TOFMS analysis of leaded IGSR particles, classification may be based on the presence of lead (Pb), antimony (Sb), and barium (Ba) just as in SEM-EDS; however, additional particle types, such as lead-copper (Pb-Cu) particles, contribute significantly (∼30%) to the leaded IGSR particle population. In lead-free IGSR particles, the dominate multi-metal particle composition found is titanium-zinc (Ti-Zn) with a conserved Zn:Ti ratio of 1.4:1, but other elements, such as copper (Cu), are also characteristic. In mixtures of the two IGSR reference materials, we were able to classify over 80% of the multi-metal particles detected with no false-positive particle-type assignments. With spICP-TOFMS, particles smaller than those typically measured by SEM-EDS are detected, with estimated median diameters for leaded and lead-free IGSR of 180 and 320 nm, respectively. Through measuring these smaller particles, up to ∼two times more particles per mL are recorded by spICP-TOFMS compared to that found by SEM-EDS. Overall, high-sensitivity and high-throughput analysis using spICP-TOFMS enables quantitative, rapid multi-elemental characterization, and classification of individual IGSR particles.