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.

We have separated carbon nanotubes through host–guest complexation using host molecules named “nanotweezers” and “nanocalipers”. In this work, a host molecule named tetragonal “M-nanobrackets”, consisting of a pair of dipyrrin nanocalipers corresponding to two brackets “[” and “]” tethered by two metals (M), is designed, synthesized, and employed to separate single-walled carbon nanotubes (SWNTs). A facile three-step process including one-pot Suzuki coupling is developed to synthesize M-nanobrackets in a 37% total yield (M = Cu). Upon extraction of SWNTs with a square nanobracket and Cu­(II), in situ formed tetragonal M-nanobrackets are found to interlock SWNTs to disperse them in 2-propanol. The interlocking is confirmed by absorption and Raman spectroscopy as well as transmission electron and atomic force microscopy. Especially, Raman spectroscopy is utilized to prove the interlocking of SWNTs; Cu-nanobrackets are found to show inherent resonance Raman signals and affect the SWNT signals, or a radial breathing vibration, due to the rigid rectangular structure of Cu-nanobrackets. The interlocking is facilely and thoroughly released through demetalation to recover the pristine SWNTs as well as the square nanobracket. Such chemically controlled locking and unlocking for SWNTs are one of the characteristics of our separation process. This enables a precise evaluation by Raman, photoluminescence, and absorption spectroscopy of the diameter selectivity to SWNTs, revealing the diameter enrichment of only three kinds of SWNTs, (7,6), (9,4), and (8,5), in the 0.02 nm diameter range from 0.90 to 0.92 nm among ∼20 kinds of SWNTs from 0.76 to 1.17 nm in their diameter range.

Strong interaction between porphyrin and nanocarbons including carbon nanotubes (CNTs) has been utilized to form stable complexes between them. We have applied the stable complex of CNTs with V- and U-shaped porphyrins and pyrenes, designated as nanotweezers and nanocalipers respectively, to separation of CNTs through their extraction to liquid phase. In order to know more about the CNT complex in liquid phase, we determined the association constants and the extraction ability of the host molecules, porphyrins, pyrenes, porphyrin- and pyrene-based nanotweezers and nanocalipers, to single-walled carbon nanotubes (SWNTs). As we expected, the order of the association constant is nanocalipers > nanotweezers > monoporphyrins > monopyrenes in the host molecules. The extraction ability of these host molecules is roughly proportional to the order of the association constants, but mismatching of the cavity size of the host and the diameter of CNTs is considered to become more apparant in liquid phase than in solid phase, destabilizing the complex in liquid phase and lowering the extraction ability.