Search Results (13)

Biomimetic nanoassemblies derived from natural products are considered promising nanomaterials due to their self-assembling ability and their favorable interactions with biological molecules leading to their numerous applications as therapeutic agents or as molecular probes. In this work, we have created peptide nanoconjugates of two natural products, β-Boswellic acid (BA) and β-glycyrrhetinic acid (GH). Both BA and GH are known for their medicinal value, including their role as strong antioxidants, anti-inflammatory, neuroprotective and as anti-tumor agents. To enhance the bioavailability of these molecules, they were functionalized with three short peptides (YYIVS, MPDAHL and GSGGL) to create six conjugates with amphiphilic structures capable of facile self-assembly. The peptides were also derived from natural sources and have been known to display antioxidant activity. Depending upon the conjugate, nanofibers, nanovesicles or a mixture of both were formed upon self-assembly. The binding interactions of the nanoconjugates with α-Synuclein, a protein implicated in Parkinson’s disease (PD) was examined through in silico studies and FTIR, circular dichroism and imaging studies. Our results indicated that the nanoassemblies interacted with alpha-synuclein fibrils efficaciously. Furthermore, the nanoassemblies were found to demonstrate high viability in the presence of microglial cells, and were found to enhance the uptake and interactions of α-Synuclein with microglial cells. The nanoconjugates designed in this work may be potentially utilized as vectors for peptide-based drug delivery or for other therapeutic applications. Full article

Among the strategies employed to overcome the development of multidrug-resistant bacteria, directed chemotherapy combined with local therapies (e.g., magnetic hyperthermia) has gained great interest. A nano-assembly coupling the antimicrobial peptide AS-48 to biomimetic magnetic nanoparticles (AS-48-BMNPs) was demonstrated to have potent bactericidal effects on both Gram-positive and Gram-negative bacteria when the antimicrobial activity of the peptide was combined with magnetic hyperthermia. Nevertheless, intracellular pathogens remain challenging due to the difficulty of the drug reaching the bacterium. Thus, improving the cellular uptake of the nanocarrier is crucial for the success of the treatment. In the present study, we demonstrate the embedding cellular uptake of the original nano-assembly into THP-1, reducing the toxicity of AS-48 toward healthy THP-1 cells. We optimized the design of PLGA[AS-48-BMNPs] in terms of size, colloidal stability, and hyperthermia activity (either magnetic or photothermal). The stability of the nano-formulation at physiological pH values was evaluated by studying the AS-48 release at this pH value. The influence of pH and hyperthermia on the AS-48 release from the nano-formulation was also studied. These results show a slower AS-48 release from PLGA[AS-48-BMNPs] compared to previous nano-formulations, which could make this new nano-formulation suitable for longer extended treatments of intracellular pathogens. PLGA[AS-48-BMNPs] are internalized in THP-1 cells where AS-48 is liberated slowly, which may be useful to treat diseases and prevent infection caused by intracellular pathogens. The treatment will be more efficient combined with hyperthermia or photothermia. Full article

Glioblastoma remains the most lethal form of brain cancer, where hybrid nanomaterials biofunctionalized with polysaccharide peptides offer disruptive strategies relying on passive/active targeting and multimodal therapy for killing cancer cells. Thus, in this research, we report for the first time the rational design and synthesis of novel hybrid colloidal nanostructures composed of gold nanoparticles stabilized by trisodium citrate (AuNP@TSC) as the oxidase-like nanozyme, coupled with cobalt-doped superparamagnetic iron oxide nanoparticles stabilized by carboxymethylcellulose ligands (Co-MION@CMC) as the peroxidase-like nanozyme. They formed inorganic–inorganic dual-nanozyme systems functionalized by a carboxymethylcellulose biopolymer organic shell, which can trigger a biocatalytic cascade reaction in the cancer tumor microenvironment for the combination of magnetothermal–chemodynamic therapy. These nanoassemblies were produced through a green aqueous process under mild conditions and chemically biofunctionalized with integrin-targeting peptide (iRDG), creating bioengineered nanocarriers. The results demonstrated that the oxidase-like nanozyme (AuNP) was produced with a crystalline face-centered cubic nanostructure, spherical morphology (diameter = 16 ± 3 nm), zeta potential (ZP) of −50 ± 5 mV, and hydrodynamic diameter (D_H) of 15 ± 1 nm. The peroxide-like nanostructure (POD, Co-MION@CMC) contained an inorganic crystalline core of magnetite and had a uniform spherical shape (2R = 7 ± 1 nm) which, summed to the contribution of the CMC shell, rendered a hydrodynamic diameter of 45 ± 4 nm and a negative surface charge (ZP = −41 ± 5 mV). Upon coupling both nanozymes, water-dispersible colloidal supramolecular vesicle-like organic–inorganic nanostructures were produced (AuNP//Co-MION@CMC, ZP = −45 ± 4 mV and D_H = 28 ± 3 nm). They confirmed dual-nanozyme cascade biocatalytic activity targeted by polymer–peptide conjugates (AuNP//Co-MION@CMC_iRGD, ZP = −29 ± 3 mV and D_H = 60 ± 4 nm) to kill brain cancer cells (i.e., bioenergy “starvation” by glucose deprivation and oxidative stress through reactive oxygen species generation), which was boosted by the magneto-hyperthermotherapy effect when submitted to the alternating magnetic field (i.e., induced local thermal stress by “nanoheaters”). This groundwork offers a wide avenue of opportunities to develop innovative theranostic nanoplatforms with multiple integrated functionalities for fighting cancer and reducing the harsh side effects of conventional chemotherapy. Full article

Self-assembling π-conjugated systems constitute efficient building blocks for the construction of supramolecular structures with tailored functional properties. In this context, perylene diimide (PDI) has attracted attention owing to its chemical robustness, thermal and photo-stability, and outstanding optical and electronic properties. Recently, the conjugation of PDI derivatives to biological molecules, including oligonucleotides and peptides, has opened new avenues for the design of nanoassemblies with unique structures and functionalities. In the present review, we offer a comprehensive summary of supramolecular bio-assemblies based on PDI. After briefly presenting the physicochemical, structural, and optical properties of PDI derivatives, we discuss the synthesis, self-assembly, and applications of PDI bioconjugates. Full article

Over various scientific fields in biochemistry, amino acids have been highlighted in research works. Protein, peptide- and amino acid-based drug delivery systems have proficiently transformed nanotechnology via immense flexibility in their features for attaching various drug molecules and biodegradable polymers. In this regard, novel nanostructures including carbon nanotubes, electrospun carbon nanofibers, gold nanoislands, and metal-based nanoparticles have been introduced as nanosensors for accurate detection of these organic compounds. These nanostructures can bind the biological receptor to the sensor surface and increase the surface area of the working electrode, significantly enhancing the biosensor performance. Interestingly, protein-based nanocarriers have also emerged as useful drug and gene delivery platforms. This is important since, despite recent advancements, there are still biological barriers and other obstacles limiting gene and drug delivery efficacy. Currently available strategies for gene therapy are not cost-effective, and they do not deliver the genetic cargo effectively to target sites. With rapid advancements in nanotechnology, novel gene delivery systems are introduced as nonviral vectors such as protein, peptide, and amino acid-based nanostructures. These nano-based delivery platforms can be tailored into functional transformation using proteins and peptides ligands based nanocarriers, usually overexpressed in the specified diseases. The purpose of this review is to shed light on traditional and nanotechnology-based methods to detect amino acids, peptides, and proteins. Furthermore, new insights into the potential of amino protein-based nanoassemblies for targeted drug delivery or gene transfer are presented. Full article

Concerns associated with nanocarriers’ therapeutic efficacy and side effects have led to the development of strategies to advance them into targeted and responsive delivery systems. Owing to their bioactivity and biocompatibility, peptides play a key role in these strategies and, thus, have been extensively studied in nanomedicine. Peptide-based nanocarriers, in particular, have burgeoned with advances in purely peptidic structures and in combinations of peptides, both native and modified, with polymers, lipids, and inorganic nanoparticles. In this review, we summarize advances on peptides promoting gene delivery systems. The efficacy of nucleic acid therapies largely depends on cell internalization and the delivery to subcellular organelles. Hence, the review focuses on nanocarriers where peptides are pivotal in ferrying nucleic acids to their site of action, with a special emphasis on peptides that assist anionic, water-soluble nucleic acids in crossing the membrane barriers they encounter on their way to efficient function. In a second part, we address how peptides advance nanoassembly delivery tools, such that they navigate delivery barriers and release their nucleic acid cargo at specific sites in a controlled fashion. Full article

The synergy between directed chemotherapy and thermal therapy (both magnetic hyperthermia and photothermia) mediated by a nanoassembly composed of functionalized biomimetic magnetic nanoparticles (BMNPs) with the chemotherapeutic drug doxorubicin (DOXO) covered by the polymer poly(lactic-co-glycolic acid) (PLGA), decorated with TAT peptide (here referred to as TAT–PLGA(DOXO-BMNPs)) is explored in the present study. The rationale behind this nanoassembly lies in an optimization of the nanoformulation DOXO-BMNPs, already demonstrated to be more efficient against tumor cells, both in vitro and in vivo, than systemic traditional therapies. By embedding DOXO-BMNPs into PLGA, which is further functionalized with the cell-penetrating TAT peptide, the resulting nanoassembly is able to mediate drug transport (using DOXO as a drug model) and behaves as a hyperthermic agent (induced by an alternating magnetic field (AMF) or by laser irradiation with a laser power density of 2 W/cm²). Our results obtained using the HepG2 cell line show that there is a synergy between chemotherapy and thermal therapy that results in a stronger cytotoxic effect when compared to that caused by the soluble DOXO. This is probably due to the enhanced DOXO release occurring upon the application of the thermal therapy, as well as the induced local temperature rise mediated by BMNPs in the nanoassembly following exposition to AMF or to near-infrared (NIR) laser irradiation. These results represent a proof of concept demonstrating that TAT–PLGA(DOXO-BMNPs) can be used to efficiently combine therapies against tumor cells, which is a step forward in the transition from systemic to local treatments. Full article

Despite being a mainstay of clinical cancer treatment, chemotherapy is limited by its severe side effects and inherent or acquired drug resistance. Nanotechnology-based drug-delivery systems are widely expected to bring new hope for cancer therapy. These systems exploit the ability of nanomaterials to accumulate and deliver anticancer drugs at the tumor site via the enhanced permeability and retention effect. Here, we established a novel drug-delivery nanosystem based on amphiphilic peptide dendrimers (AmPDs) composed of a hydrophobic alkyl chain and a hydrophilic polylysine dendron with different generations (AmPD KK₂ and AmPD KK₂K₄). These AmPDs assembled into nanoassemblies for efficient encapsulation of the anti-cancer drug doxorubicin (DOX). The AmPDs/DOX nanoformulations improved the intracellular uptake and accumulation of DOX in drug-resistant breast cancer cells and increased permeation in 3D multicellular tumor spheroids in comparison with free DOX. Thus, they exerted effective anticancer activity while circumventing drug resistance in 2D and 3D breast cancer models. Interestingly, AmPD KK₂ bearing a smaller peptide dendron encapsulated DOX to form more stable nanoparticles than AmPD KK₂K₄ bearing a larger peptide dendron, resulting in better cellular uptake, penetration, and anti-proliferative activity. This may be because AmPD KK₂ maintains a better balance between hydrophobicity and hydrophilicity to achieve optimal self-assembly, thereby facilitating more stable drug encapsulation and efficient drug release. Together, our study provides a promising perspective on the design of the safe and efficient cancer drug-delivery nanosystems based on the self-assembling amphiphilic peptide dendrimer. Full article

Magnetococcus marinus magnetosome-associated protein MamC, expressed as recombinant, has been proven to mediate the formation of novel biomimetic magnetic nanoparticles (BMNPs) that are successful drug nanocarriers for targeted chemotherapy and hyperthermia agents. These BMNPs present several advantages over inorganic magnetic nanoparticles, such as larger sizes that allow the former to have larger magnetic moment per particle, and an isoelectric point at acidic pH values, which allows both the stable functionalization of BMNPs at physiological pH value and the molecule release at acidic (tumor) environments, simply based on electrostatic interactions. However, difficulties for BMNPs cell internalization still hold back the efficiency of these nanoparticles as drug nanocarriers and hyperthermia agents. In the present study we explore the enhanced BMNPs internalization following upon their encapsulation by poly (lactic-co-glycolic) acid (PLGA), a Food and Drug Administration (FDA) approved molecule. Internalization is further optimized by the functionalization of the nanoformulation with the cell-penetrating TAT peptide (TATp). Our results evidence that cells treated with the nanoformulation [TAT-PLGA(BMNPs)] show up to 80% more iron internalized (after 72 h) compared to that of cells treated with BMNPs (40%), without any significant decrease in cell viability. This nanoformulation showing optimal internalization is further characterized. In particular, the present manuscript demonstrates that neither its magnetic properties nor its performance as a hyperthermia agent are significantly altered due to the encapsulation. In vitro experiments demonstrate that, following upon the application of an alternating magnetic field on U87MG cells treated with BMNPs and TAT-PLGA(BMNPs), the cytotoxic effect of BMNPs was not affected by the TAT-PLGA enveloping. Based on that, difficulties shown in previous studies related to poor cell uptake of BMNPs can be overcome by the novel nanoassembly described here. Full article

Protein fibrils characterized with a cross-β-sheet quaternary structure have gained interest as nanomaterials in biomedicine, including in the design of subunit vaccines. Recent studies have shown that by conjugating an antigenic determinant to a self-assembling β-peptide, the resulting supramolecular assemblies act as an antigen delivery system that potentiates the epitope-specific immune response. In this study, we used a ten-mer self-assembling sequence (I₁₀) derived from an amyloidogenic peptide to biophysically and immunologically characterize a nanofibril-based vaccine against the influenza virus. The highly conserved epitope from the ectodomain of the matrix protein 2 (M2e) was elongated at the N-terminus of I₁₀ by solid phase peptide synthesis. The chimeric M2e-I₁₀ peptide readily self-assembled into unbranched, long, and twisted fibrils with a diameter between five and eight nm. These cross-β nanoassemblies were cytocompatible and activated the heterodimeric Toll-like receptor (TLR) 2/6. Upon mice subcutaneous immunization, M2e-fibrils triggered a robust anti-M2e specific immune response, which was dependent on self-assembly and did not require the use of an adjuvant. Overall, this study describes the efficacy of cross-β fibrils to activate the TLR 2/6 and to stimulate the epitope-specific immune response, supporting usage of these proteinaceous assemblies as a self-adjuvanted delivery system for antigens. Full article

Graphene oxide (GO) is a bidimensional novel material that exhibits high biocompatibility and angiogenic properties, mostly related to the intracellular formation of reactive oxygen species (ROS). In this work, we set up an experimental methodology for the fabrication of GO@peptide hybrids by the immobilization, via irreversible physical adsorption, of the Ac-(GHHPH)₄-NH₂ peptide sequence, known to mimic the anti-angiogenic domain of the histidine-proline-rich glycoprotein (HPRG). The anti-proliferative capability of the graphene-peptide hybrids were tested in vitro by viability assays on prostate cancer cells (PC-3 line), human neuroblastoma (SH-SY5Y), and human retinal endothelial cells (primary HREC). The anti-angiogenic response of the two cellular models of angiogenesis, namely endothelial and prostate cancer cells, was scrutinized by prostaglandin E2 (PGE₂) release and wound scratch assays, to correlate the activation of inflammatory response upon the cell treatments with the GO@peptide nanocomposites to the cell migration processes. Results showed that the GO@peptide nanoassemblies not only effectively induced toxicity in the prostate cancer cells, but also strongly blocked the cell migration and inhibited the prostaglandin-mediated inflammatory process both in PC-3 and in HRECs. Moreover, the cytotoxic mechanism and the internalization efficiency of the theranostic nanoplatforms, investigated by mitochondrial ROS production analyses and confocal microscopy imaging, unraveled a dose-dependent manifold mechanism of action performed by the hybrid nanoassemblies against the PC-3 cells, with the detection of the GO-characteristic cell wrapping and mitochondrial perturbation. The obtained results pointed out to the very promising potential of the synthetized graphene-based hybrids for cancer therapy. Full article

Nanotechnology approaches play an important role in developing novel and efficient carriers for biomedical applications. Peptides are particularly appealing to generate such nanocarriers because they can be rationally designed to serve as building blocks for self-assembling nanoscale structures with great potential as therapeutic or diagnostic delivery vehicles. In this review, we describe peptide-based nanoassemblies and highlight features that make them particularly attractive for the delivery of nucleic acids to host cells or improve the specificity and sensitivity of probes in diagnostic imaging. We outline the current state in the design of peptides and peptide-conjugates and the paradigms of their self-assembly into well-defined nanostructures, as well as the co-assembly of nucleic acids to form less structured nanoparticles. Various recent examples of engineered peptides and peptide-conjugates promoting self-assembly and providing the structures with wanted functionalities are presented. The advantages of peptides are not only their biocompatibility and biodegradability, but the possibility of sheer limitless combinations and modifications of amino acid residues to induce the assembly of modular, multiplexed delivery systems. Moreover, functions that nature encoded in peptides, such as their ability to target molecular recognition sites, can be emulated repeatedly in nanoassemblies. Finally, we present recent examples where self-assembled peptide-based assemblies with “smart” activity are used in vivo. Gene delivery and diagnostic imaging in mouse tumor models exemplify the great potential of peptide nanoassemblies for future clinical applications. Full article

Morphological control of nanostructures that are composed of amphiphilic di- or tri-block molecules by external stimuli broadens their applications for molecular containers, nanoreactors, and controlled release materials. In this study, triblock amphiphiles comprising oligo(ethylene glycol), oligo(l-lysine), and tetra(l-phenylalanine) were prepared for the construction of nanostructures that can transform accompanying α-to-β transition of core-forming peptides. Circular dichroic (CD) measurements showed that the triblock amphiphiles adopted different secondary structures depending on the solvent environment: they adopt β-sheet structures in aqueous solution, while α-helix structures in 25% 2,2,2-trifluoroethanol (TFE) solution under basic pH conditions. Transmission electron microscopic (TEM) observation revealed that the triblock amphiphiles formed vesicle structures in 25% TFE aq. Solvent exchange from 25% TFE to water induced morphological transformation from vesicles to arc-shaped nanostructures accompanying α-β conformational transition. The transformable nanostructures may be useful as novel smart nanomaterials for molecular containers and micro reactors. Full article