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Goldnanoclusters (GNCs) have become a promising nanomaterial for bioimaging because of their unique optical properties and biocompatibility. In this study, lycosin-I peptide, which possesses a highly selective anticancer activity by affecting the permeability of cancer cell membrane, was firstly modified for constructing fluorescent GNCs (LGNCs) for bioimaging of tumor cells. The obtained LGNCs exhibited strong near-infrared (NIR) fluorescence, which can be further enhanced by the peptide-induced aggregation and selectively stained three cancerous cell lines over normal cell lines with low intrinsic toxicity. After uptake by tumor cells, LGNC aggregates can be depolymerized into ultrasmall nanoclusters by high-level glutathione (GSH) and realize the nuclear targeting translocation. Collectively, our work suggests the potential of natural active biomolecules in designing NIR fluorescent GNCs for bioimaging.

Cell penetrating peptides (CPPs) are commonly utilized for intracellular delivery of functional materials to circumvent biomembrane barrier. However, further application of CPPs is hindered by lacking selectivity toward targeted cells. The spider venom peptide, lycosin-I, is a CPP with potent cytotoxicity to cancer cells, which might enable lycosin-I to deliver functional materials into cancer cells selectively. In this study, we demonstrated that the lycosin-I-conjugated spherical gold nanoparticles (LGNPs) not only exhibited efficient cellular internalization efficiency toward cancer cells but also displayed unprecedented selectivity over noncancerous cells. Although LGNPs were removed from the living circulatory system via reticuloendothelial system-dominant clearance modes without noticeable adverse effects to animals, they actually displayed active tumor-targeting effects and efficient accumulation in tumors in vivo. Furthermore, the potential application of this platform for cancer therapy was explored by lycosin-I-conjugated gold nanorods (LGNRs). LGNRs exhibited selective intracellular translocation towards cancer cells and efficient photothermal effect under near infrared (NIR, 808 nm) irradiation, which consequently killed cancer cells in vitro and in vivo effectively. Therefore, the established LGNPs and LGNRs possessed great potential in cancer-targeting delivery and photothermal therapy.

Lycosin-I, a peptide toxin derived from spider venom, has been demonstrated to be a promising candidate for the inhibition of tumor cell growth in vitro and in vivo by interacting with and penetrating the cell membrane. Owing to the shortage of an efficient characterization strategy, however, there is still a lack of detailed knowledge about the distribution of the stoichiometric composition information on this peptide in solution and on lipid membrane prior to the cellular uptake process, which is fundamentally important for the understanding of the anticancer mechanism. In this work, with objective-type total internal reflection fluorescence microscopy (TIRF), the distribution of the stoichiometric composition of lycosin-I in different solutions as well as on the lipid membrane was explored extensively on the basis of a statistical single molecule fluorescence intensity analysis for the first time. It was found that lycosin-I is mainly present in a monomer state in diverse physiological solutions regardless of the concentration of the peptide and the incubation time. However, on the lipid membrane, the fraction of small size oligomers increased as a function of time. Fusion of movable peptide molecules to those peptide oligomers with restricted motion on the lipid membrane was also observed.