LC-AMP-F1 Derived from the Venom of the Wolf Spider Lycosa coelestis, Exhibits Antimicrobial and Antibiofilm Activities.

In recent years, there has been a growing interest in antimicrobial peptides as innovative antimicrobial agents for combating drug-resistant bacterial infections, particularly in the fields of biofilm control and eradication. In the present study, a novel cationic antimicrobial peptide, named LC-AMP-F1, was derived from the cDNA library of the Lycosa coelestis venom gland. The sequence, physicochemical properties and secondary structure of LC-AMP-F1 were predicted and studied. LC-AMP-F1 was tested for stability, cytotoxicity, drug resistance, antibacterial activity, and antibiofilm activity in vitro compared with melittin, a well-studied antimicrobial peptide. The findings indicated that LC-AMP-F1 exhibited inhibitory effects on the growth of various bacteria, including five strains of multidrug-resistant bacteria commonly found in clinical settings. Additionally, LC-AMP-F1 demonstrated effective inhibition of biofilm formation and disruption of mature biofilms. Furthermore, LC-AMP-F1 exhibited favorable stability, minimal hemolytic activity, and low toxicity towards different types of eukaryotic cells. Also, it was found that the combination of LC-AMP-F1 with conventional antibiotics exhibited either synergistic or additive therapeutic benefits. Concerning the antibacterial mechanism, scanning electron microscopy and SYTOX Green staining results showed that LC-AMP-F1 increased cell membrane permeability and swiftly disrupted bacterial cell membranes to exert its antibacterial effects. In summary, the findings and studies facilitated the development and clinical application of novel antimicrobial agents.

The Recent Development of Multifunctional Gold Nanoclusters in Tumor Theranostic and Combination Therapy.

The rising incidence and severity of malignant tumors threaten human life and health, and the current lagged diagnosis and single treatment in clinical practice are inadequate for tumor management. Gold nanoclusters (AuNCs) are nanomaterials with small dimensions (≤3 nm) and few atoms exhibiting unique optoelectronic and physicochemical characteristics, such as fluorescence, photothermal effects, radiosensitization, and biocompatibility. Here, the three primary functions that AuNCs play in practical applications, imaging agents, drug transporters, and therapeutic nanosystems, are characterized. Additionally, the promise and remaining limitations of AuNCs for tumor theranostic and combination therapy are discussed. Finally, it is anticipated that the information presented herein will serve as a supply for researchers in this area, leading to new discoveries and ultimately a more widespread use of AuNCs in pharmaceuticals.

Antibacterial Potential Analysis of Novel α-Helix Peptides in the Chinese Wolf Spider Lycosa sinensis.

The spider Lycosa sinensis represents a burrowing wolf spider (family Lycosidae) widely distributed in the cotton region of northern China, whose venom is rich in various bioactive peptides. In previous study, we used a combination strategy of peptidomic and transcriptomic analyses to systematically screen and identify potential antimicrobial peptides (AMPs) in Lycosa sinensis venom that matched the α-helix structures. In this work, the three peptides (LS-AMP-E1, LS-AMP-F1, and LS-AMP-G1) were subjected to sequence analysis of the physicochemical properties and helical wheel projection, and then six common clinical pathogenic bacteria (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) with multiple drug-resistance were isolated and cultured for the evaluation and analysis of antimicrobial activity of these peptides. The results showed that two peptides (LS-AMP-E1 and LS-AMP-F1) had different inhibitory activity against six clinical drug-resistant bacteria; they can effectively inhibit the formation of biofilm and have no obvious hemolytic effect. Moreover, both LS-AMP-E1 and LS-AMP-F1 exhibited varying degrees of synergistic therapeutic effects with traditional antibiotics (azithromycin, erythromycin, and doxycycline), significantly reducing the working concentration of antibiotics and AMPs. In terms of antimicrobial mechanisms, LS-AMP-E1 and LS-AMP-F1 destroyed the integrity of bacterial cell membranes in a short period of time and completely inhibited bacterial growth within 10 min of action. Meanwhile, high concentrations of Mg2+ effectively reduced the antibacterial activity of LS-AMP-E1 and LS-AMP-F1. Together, it suggested that the two peptides interact directly on bacterial cell membranes. Taken together, bioinformatic and functional analyses in the present work sheds light on the structure-function relationships of LS-AMPs, and facilitates the discovery and clinical application of novel AMPs.

Hollow Mesoporous CeO2-Based Nanoenzymes Fabrication for Effective Synergistic Eradication of Malignant Breast Cancer via Photothermal-Chemodynamic Therapy.

CeO2-based nanoenzymes present a very promising paradigm in cancerous therapy, as H2O2 can be effectively decomposed under the electron transmit between Ce3+ and Ce4+. However, the limitations of endogenous H2O2 and intracellular low Fenton-like reaction rate lead to single unsatisfied chemodynamic therapy (CDT) efficacy. Other therapeutic modalities combined with chemodynamic therapy are generally used to enhance the tumor eradiation efficacy. Here, we have synthesized a novel hollow pH-sensitive CeO2 nanoenzyme after a cavity is loaded with indocyanine green (ICG), as well as with surface modification of tumor targeting peptides, Arg-Gly-Asp (denoted as HCeO2@ICG-RGD), to successfully target tumor cells via αvß3 recognition. Importantly, in comparison with single chemodynamic therapy, a large amount of reactive oxygen species in cytoplasm were induced by enhanced chemodynamic therapy with photothermal therapy (PTT). Furthermore, tumor cells were efficiently killed by a combination of photothermal and chemodynamic therapy, revealing that synergistic therapy was successfully constructed. This is mainly due to the precise delivery of ICG and release after HCeO2 decomposition in cytoplasm, in which effective hyperthermia generation was found under 808 nm laser irradiation. Meanwhile, our HCeO2@ICG-RGD can act as a fluorescent imaging contrast agent for an evaluation of tumor tissue targeting capability in vivo. Finally, we found that almost all tumors in HCeO2@ICG-RGD+laser groups were completely eradicated in breast cancer bearing mice, further proving the effective synergistic effect in vivo. Therefore, our novel CeO2-based PTT agents provide a proof-of-concept argumentation of tumor-precise multi-mode therapies in preclinical applications.

Spider Toxin Peptide-Induced NIR Gold Nanocluster Fabrication for GSH-Responsive Cancer Cell Imaging and Nuclei Translocation.

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.

Crucial Breakthrough of Functional Persistent Luminescence Materials for Biomedical and Information Technological Applications.

Persistent luminescence is a phenomenon in which luminescence is maintained for minutes to hours without an excitation source. Owing to their unique optical properties, various kinds of persistent luminescence materials (PLMs) have been developed and widely employed in numerous areas, such as bioimaging, phototherapy, data-storage, and security technologies. Due to the complete separation of two processes, -excitation and emission-, minimal tissue absorption, and negligible autofluorescence can be obtained during biomedical fluorescence imaging using PLMs. Rechargeable PLMs with super long afterglow life provide novel approaches for long-term phototherapy. Moreover, owing to the exclusion of external excitation and the optical rechargeable features, multicolor PLMs, which have higher decoding signal-to-noise ratios and high storage capability, exhibited an enormous application potential in information technology. Therefore, PLMs have significantly promoted the application of optics in the fields of multimodal bioimaging, theranostics, and information technology. In this review, we focus on the recently developed PLMs, including inorganic, organic and inorganic-organic hybrid PLMs to demonstrate their superior applications potential in biomedicine and information technology.

Spider Toxin Peptide Lycosin-I Functionalized Gold Nanoparticles for in vivo Tumor Targeting and Therapy.

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.

Quantifying the Distribution of the Stoichiometric Composition of Anticancer Peptide Lycosin-I on the Lipid Membrane with Single Molecule Spectroscopy.

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.

A survey of the venom of the spider Lycosa vittata by biochemical, pharmacological and transcriptomic analyses.

Lycosa vittata, mainly distributed in the southwest of China, is a medium-sized and venomous spider, whose venom remains unexplored so far. This study aims to present an overview of the venom. It mainly consisted of diverse peptides and exhibited inhibitory effects on voltage-gated ion channels in rat dorsal root ganglia neurons, with a strongest inhibition on tetrodotoxin-sensitive and tetrodotoxin-resistant voltage-gated Na(+) channels. Interestingly, it exerted cytotoxicity to cancer cells, with approximately 10-fold selectivity on PC-3 over others, implying the existence of selective anti-PC-3 agents in the venom. Moreover, 51 toxin-like peptides were deduced from the venom gland transcriptome. Bioinformatic analyses suggested their structures might have some distinguished properties and their predicted functions were consistent with the venom activities. This study suggests that the venom is an attractive source of neurotoxins with therapeutic significance, and provides references for the structure and function investigation of specific toxins in the future.