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.

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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.

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.