Xinglu Huang

In our previous study we reported that the interaction of nanoparticles with cells can be influenced by particle shape, but until now the effect of particle shape on in vivo behavior remained poorly understood. In the present study, we control the fabrication of fluorescent mesoporous silica nanoparticles (MSNs) by varying the concentration of reaction reagents especially to design a series of shapes. Two different shaped fluorescent MSNs (aspect ratios, 1.5, 5) were specially designed, and the effects of particle shape on biodistribution, clearance and biocompatibility in vivo were investigated. Organ distributions show that intravenously administrated MSNs are mainly present in the liver, spleen and lung (>80%) and there is obvious particle shape effects on in vivo behaviors. Short-rod MSNs are easily trapped in the liver, while long-rod MSNs distribute in the spleen. MSNs with both aspect ratios have a higher content in the lung after PEG modification. We also found MSNs are mainly excreted by urine and feces, and the clearance rate of MSNs is primarily dependent on the particle shape, where short-rod MSNs have a more rapid clearance rate than long-rod MSNs in both excretion routes. Hematology, serum biochemistry, and histopathology results indicate that MSNs would not cause significant toxicity in vivo, but there is potential induction of biliary excretion and glomerular filtration dysfunction. These findings may provide useful information for the design of nanoscale delivery systems and the environmental fate of nanoparticles.

The emergence of photoluminescent carbon-based nanomaterials has shown exciting potential in the development of benign nanoprobes. However, the in vivo 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 in vivo 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 in vivo behavior of nanoplatforms under various injection routes, an important step forward toward safety and efficacy analysis of nanoparticles.

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.