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Antimicrobial pentatopic 2,2′:6′,2′′-terpyridines that form 3-D supramolecular hexagonal prisms with Cd 2+ through coordination driven self-assembly can be entrapped by lipid discoidal bicelles, composed of 1,2-dipalmitoyl- sn-glycero -3-phosphocholine, 1,2-dihexanoyl- sn-glycero -3-phosphocholine and 1,2-dipalmitoyl- sn-glycero -3-phospho-(1′-rac-glycerol) lipid, forming a well-defined nanocomplex. Structural characterization performed by very small angle neutron scattering, small angle X-ray scattering and transmission electron microscopy suggests that the hexagonal prisms are preferably located at the rim of bicellar discs with the hexagonal face in parallel with the bilayers, instead of face-to-face stacking. Such a configuration reduces the π−π interaction and consequently enhances the fluorescence emission. Since novel supramolecules were reported to have antibiotic functions, this study provides insight into the interactions of antimicrobial supermolecules with lipid membranes, leading to potential theranostic applications. 

The authors designed a structurally stable nano-in-nano (NANO2) system highly capable of bioimaging via an aggregation-enhanced NIR excited emission and photoacoustic response achieved based on atomically precise gold nanoclusters protected by linear thiolated ligands [Au25(SCnH2n+1)18, n = 4–16] encapsulated in discoidal phospholipid bicelles through a one-pot synthesis. The detailed morphological characterization of NANO2 is conducted using cryogenic transmission electron microscopy, small/wide angle X-ray scattering with the support of molecular dynamics simulations, providing information on the location of Au nanoclusters in NANO2. The photoluminescence observed for NANO2 is 20–60 times more intense than that of the free Au nanoclusters, with both excitation and emission wavelengths in the near-infrared range, and the photoacoustic signal is more than tripled. The authors attribute this newly discovered aggregation enhanced photoluminescence and photoacoustic signals to the restriction of intramolecular motion of the clusters’ ligands. With the advantages of biocompatibility and high cellular uptake, NANO2 is potentially applicable for both in vitro and in vivo imaging, as the authors demonstrate with NIR excited emission from in vitro A549 human lung and the KB human cervical cancer cells. 

Peptide nucleic acids (PNAs) have gained considerable attention due to their remarkable potential in gene editing and targeting-based strategies. However, cellular delivery of PNAs remains a challenge in developing their broader therapeutic applications. Here, we investigated a novel complex made of lipid bicelles and PNA-based carriers for the efficient delivery of PNAs. For proof of concept, PNAs targeting microRNA (miR) 210 and 155 were tested. Comprehensive evaluation of positive as well as negative charge-containing bicelles with PNA : lipid ratios of 1 : 100, 1 : 1000, and 1 : 2500 was performed. The negatively charged bicelles with a PNA : lipid molar ratio of 1 : 2500 yielded a discoidal shape with a uniform diameter of ∼30 nm and a bilayer thickness of 5 nm, while the positively charged bicellar system contained irregular vesicles after the incorporation of PNA. Small-angle X-ray scattering (SAXS) analysis was performed to provide insight into how the hydrophobic PNAs interact with bicelles. Further, flow cytometry followed by confocal microscopy analyses substantiate the superior transfection efficiency of bicelles containing dye-conjugated antimiR PNAs. Functional analysis also confirmed miR inhibition by PNA oligomers delivered by bicelles. The nanodiscoidal complex opens a new pathway to deliver PNAs, which, on their own, are a great challenge to be endocytosed into cells. 

Poly(amino acid)-coated gold nanoparticles hold promise in biomedical applications, particularly because they combine the unique physicochemical properties of the gold core, excellent biocompatibility, and easy functionalization of the poly(amino acid)-capping shell. Here we report a novel method for the preparation of robust hybrid core–shell nanosystems consisting of a Au 144 cluster and a densely grafted polylysine layer. Linear polylysine chains were grown by direct N -carboxyanhydride (NCA) polymerization onto ligands capping the gold nanocluster. The density of the polylysine chains and the thickness of the polymer layer strongly depend on the amount and concentration of the NCA monomer and the initiator. The optical spectra of the so-obtained core–shell nanosystems show a strong surface plasmon resonance (SPR)-like band at 531 nm. In fact, despite maintenance of the gold cluster size and the absence of interparticle aggregation, the polylysine-capped clusters behave as if they have a diameter nearly 4 times larger. To the best of our knowledge, this is the first observation of the growth of a fully developed, very stable SPR-like band for a gold nanocluster of such dimensions. The robust polylysine protective shell makes the nanoparticles very stable under conditions of chemical etching, in the presence of glutathione, and at different pH values, without gold core deshielding or alteration of the SPR-like band. This polymerization method can conceivably be extended to prepare core–shell nanosystems based on other mono- or co-poly(amino acids).