Fluorescent quantum dots (QDs) have great potential for in vivo biomedical imaging and diagnostic applications. However, these nanoparticles are composed of heavy metals and are very small in diameter, and their possible toxicity must therefore be considered. As yet, no studies have reported the transfer of QDs between mother and fetus. The transfer of CdTe/CdS QDs of different sizes and dosages, and with different outer capping materials, from pregnant mice to fetuses is investigated. It is shown that QDs may be transferred from female mice to their fetuses across the placental barrier. Smaller QDs are more easily transferred than larger QDs and the number of QDs transferred increases with increasing dosage. Capping with an inorganic silica shell or organic polyethylene glycol reduces QD transfer but does not eliminate it. These results suggest that the clinical utility of QDs could be limited in pregnant women.

Upon contact with biofluids, proteins are quickly adsorbed onto the nanoparticle (NP) surface to form a protein corona, which initiates the opsonization and facilitates the rapid clearance of the NP by macrophage uptake. Although polyethylene glycol (PEG) functionalization has been the standard approach to evade macrophage uptake by reducing protein adsorption, it cannot fully eliminate nonspecific uptake. Herein, polyglycerol (PG) grafting is demonstrated as a better alternative to PEG. NPs of various size and material were grafted with PG and PEG at 30, 20, and 10 wt % contents by controlling the reaction conditions, and the resulting NP-PG and NP-PEG were characterized qualitatively by IR spectroscopy and quantitatively by thermogravimetric analysis. Their resistivity to adsorption of the proteins in fetal bovine serum and human plasma were compared by polyacrylamide gel electrophoresis, bicinchoninic acid assay, and liquid chromatography-tandem mass spectrometry, giving a consistent conclusion that PG shields protein adsorption more efficiently than does PEG. The macrophage uptake was assayed by transmission electron microscopy and by extinction spectroscopy or inductively coupled plasma mass spectrometry, revealing that PG avoids macrophage uptake more efficiently than does PEG. In particular, a NP coated with PG at 30 wt % (NP-PG-h) prevents corona formation almost completely, regardless of NP size and core material, leading to the complete evasion of macrophage uptake. Our findings demonstrate that PG grafting is a promising strategy in nanomedicine to improve anti-biofouling property and stealth efficiency in nanoformulations.

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Preferential accumulation of nanoparticles in a tumor is realized commonly by combined effects of active and passive targeting. However, passive targeting based on an enhanced permeation and retention (EPR) effect is not sufficient to observe clear tumor fluorescence images in most of the in vivo experiments using tumor‐bearing mice. Herein, polyglycerol‐functionalized nanodiamonds (ND‐PG) conjugated with cyanine dye (Cy7) are synthesized and it is found that the resulting ND‐PG‐Cy7 is preferentially accumulated in the tumor, giving clear fluorescence in in vivo and ex vivo fluorescence images. One of the plausible reasons is the longer in vivo blood circulation time of ND‐PG‐Cy7 (half‐life: 58 h determined by the pharmacokinetic analysis) than that of other nanoparticles (half‐life: <20 h in most of the previous reports). In a typical example, the fluorescence intensity of tumors increases due to continuous tumor accumulation of ND‐PG‐Cy7, even more than one week postinjection. This may be owing to the stealth effect of PG that was reported previously, avoiding recognition and excretion by reticuloendothelial cells, which are abundant in liver and spleen. In fact, the fluorescence intensities from the liver and spleen is similar to those from other organs, while the tumor exhibits much stronger fluorescence in the ex vivo image.

Functionalization of nanoparticles (NPs) with targeting moieties has a high potential to advance precision nanomedicine. However, the targeting moieties on a NP surface are known to be masked by a protein corona in biofluids, lowering the targeting efficiency. Although it has been demonstrated at the cellular level, little is known about the influence of the protein corona on the subcellular targeting. Herein, we adopted triphenylphosphonium (TPP) as a mitochondrial targeting moiety and investigated the effects of protein coronas from fetal bovine serum and human plasma on its targeting ability and cytotoxicity. Specifically, we introduced TPP in low (l) and high (h) densities on the surface of nanodiamond (ND) functionalized with polyglycerol (PG). Despite the "corona-free" PG interface, we found that the TPP moiety attracted proteins to form a corona layer with clear linearity between the TPP density and the protein amount. By performing investigations on human cervix epithelium (HeLa) and human lung epithelial carcinoma (A549) cells, we further demonstrated that (1) the protein corona alleviated the cytotoxicity of both ND-PG-TPP-l and -h, (2) a smaller amount of proteins on the surface of ND-PG-TPP-l did not affect its mitochondrial targeting ability, and (3) a larger amount of proteins on the surface of ND-PG-TPP-h diminished its targeting specificity by restricting the NDs inside the endosome and lysosome compartments. Our findings will provide in-depth insights into the design of NPs with active targeting moiety for more precise and safer delivery at the subcellular level.