We have experimentally observed around 2 orders of magnitude circular dichroism (CD) enhancement in the visible region for cysteine molecules located in the hotspots of gold nanosphere clusters. The observed plasmon-induced CD responses show a significant correlation with the chiral nature of molecules at the hotspots. These results provide a concrete experimental demonstration on the predicted chiroptical transfer and amplification effect that arises from hotspot-mediated exciton−plasmon interactions in a strongly coupled metallic nanostructure, even though the exciton−plasmon coupling works at a far off-resonant regime. Our findings suggest here that plasmonic hotspot-based CD amplifier may provide a new strategy for ultrasensitive detection and quantification of molecular chiralitya key aspect for various bioscience and biomedicine applications.

One of the major challenges in current cancer therapy is to maximize therapeutic effect and evaluate tumor progression under the scheduled treatment protocol. To address these challenges, we synthesized the cytotoxic peptide (KLAKLAK)2 (named KLAK) conjugated amphiphilic poly(β-thioester)s copolymers (H-P-K) composed of reactive oxygen species (ROS) sensitive backbones and hydrophilic polyethylene glycol (PEG) side chains. H-P-K could self-assemble into micelle-like nanoparticles by hydrophobic interaction with copolymer backbones as cores and PEG and KLAK as shells. The assembled polymer-peptide nanoparticles remarkably improved cellular internalization and accumulation of therapeutic KLAK in cells. Compared to free KLAK peptide, the antitumor activity of H-P-K was significantly enhanced up to ∼400 times, suggesting the effectiveness of the nanoscaled polymer-peptide conjugation as biopharmaceuticals. The higher antitumor activity of nanoparticles was attributed to the efficient disruption of mitochondrial membranes and subsequent excessive ROS production in cells. To realize the ROS monitoring and treatment evaluation, we encapsulated squaraine (SQ) dyes as built-in reporters in ROS-sensitive H-P-K micelles. The overgenerated ROS around mitochondria stimulated the swelling of nanoparticles and subsequent release of SQ, which formed H-aggregates and significantly increased the photoacoustic (PA) signal. We believed that this self-assembled polymer-peptide nanotherapeutics incorporating built-in reporters has great potential for high antitumor performance and in situ treatment evaluation.

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Six surfactant-like peptides with the same amino acid composition but different primary sequences are designed, including GAVIK, KIVAG, IVAGK, KGAVI, VGIAK, and KAIGV. These peptides form antiparallel β-sheets during self-assembly. Because the constituent residues have different side chain size and hydrophobicity, sequence changes adjust group distribution and hydrophobicity on the two sides of a given β-sheet. This consequently tunes the binding energy of the side-to-side pairing conformations and leads to different self-assembled structures. GAVIK and KIVAG form short nanorods with diameters of 8.5 ± 1.0 nm and lengths <150 nm. IVAGK and KGAVI form nanosheets with heights of 4.0 ± 0.5 nm and limited lengths and widths. VGIAK and KAIGV form long fibrils with diameters of 7.0 ± 1.0 nm and lengths of micrometer scale. These nanostructures exhibit different capacity in encapsulating insoluble hydrophobic drug molecules and delivering them into the cells. The nanosheets of IVAGK and KGAVI can encapsulate both nile red and doxorubicin molecules to an extent of up to 17-23% in mole ratio. Moreover, the shape and size of the nanostructures affect the drug delivery into cells greatly, with the nanosheets and short rods exhibiting higher efficiency than the long fibrils. The study provides new insights into programmed peptide self-assembly toward specific functionalities.

Peptide nanodrugs have been developed as promising antitumor chemotherapeutics because they partially overcome the drawbacks of free peptide drugs, but insufficient tumor penetration and interference of peptide function limit their further application. In this work, we have developed multifunctional peptide conjugated dendrimers for improving tumor penetration, cancer cell-specific peptide delivery and anticancer ability. The cytotoxic peptide KLAK, cell-penetrating peptide TAT and matrix metalloproteinase 2 (MMP2)-sensitive peptide-poly(ethylene glycol) (PEG) were conjugated onto dendrimers by one-pot synthesis to gain PKT-S-PEG. The enzyme-sensitive properties and incubation stability of the dendrimers were investigated by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Moreover, the cell viability, internalization pathway, mitochondria-regulated apoptosis and tumor penetration ability were measured by CCK-8 assay, lysosome colocalization, JC-1 assay and multicellular spheroid (MCS) experiments, respectively, in human primary glioblastoma (U87) cells. PKT-S-PEG showed significantly enhanced intracellular delivery performance, antitumor efficacy and deep tumor penetration capacity compared to a control non-MMP2 sensitive dendrimer PKT-C-PEG. The MMP2-overexpressing tumor microenvironment caused deprotection by removal of PEG, resulting in the decrease of particle size and exposure of KLAK and TAT, which enhanced tumor penetration, the entry of bioactive peptides into cells and subsequently the effective disruption of mitochondria. We believe that the peptide-dendrimer conjugate has potential for specific and effective delivery of peptide-based therapeutics into tumors.

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Fungal contamination imposes threats to agriculture and food production and human health. A method to safely and effectively restrict fungal contamination is still needed. Here, we report the effect and mode of action of (E)-2-hexenal, one of the green leaf volatiles (GLVs), on the spore germination of Aspergillus flavus, which can contaminate a variety of crops. The EC 50 value, minimum inhibitory concentration (MIC), and minimum fungicidal concentration (MFC) of (E)-2-hexenal were 0.26, 1.0, and 4.0 μL/mL, respectively. As observed by scanning electron microscopy (SEM), the surface morphology of A. f lavus spores did not change after treatment with the MIC of (E)-2-hexenal, but the spores were shrunken and depressed upon treatment with the MFC of (E)-2-hexenal. The MIC and MFC of (E)-2-hexenal induced evident phosphatidylserine (PS) externalization of A. flavus spores as detected by double staining with Annexin V-FITC and propidium iodide, indicating that early apoptosis was potentially induced. Furthermore, sublethal doses of (E)-2-hexenal disturbed pyruvate metabolism and reduced the intracellular soluble protein content of A. flavus spores during the early stage of germination, and MIC treatment decreased acetyl-CoA and ATP contents by 65.7 ± 3.7% and 53.9 ± 4.0% (P < 0.05), respectively. Additionally, the activity of mitochondrial dehydrogenases was dramatically inhibited by 23.8 ± 2.2% (P < 0.05) at the MIC of (E)-2-hexenal. Therefore, the disruption of mitochondrial energy metabolism and the induction of early apoptosis are involved in the mechanism of action of (E)-2-hexenal against A. flavus spore germination.

Reversible photocontrol of dynamic chirality in self-assembly systems is of great importance in exploitations of artificial nanomachines for scientific and industrious applications. Here, a new strategy is proposed for achieving optically chiral controls based on photoswitchable plasmonic nanostructures. Chiral plasmonic nanoassemblies that are responsive to optomechanical perturbations exerted by circular polarized light (CPL) in the visible (vis)/ near infrared (NIR) region are designed. The reversible photoswitching between opposite chiral states is verified by circular dichroism (CD) spectral signals. Theoretical simulations reveal the key role of optical torques in driving this chiral switching. By regulating light polarization or tuning light frequency to excite different plasmonic modes of the nanostructures, such an optomechanically driven chiral switching can enable a directed mirrorsymmetry breaking and selective chiral amplification in nanoassemblies. This plasmon-based photoswitching nanosystem can operate at the optical transparent window, showing particular advantages over most of the molecular photoswitches for applications in living systems.