Gold nanostructures: synthesis, properties, and neurological applications.

Recent advances in technology are expected to increase our current understanding of neuroscience. Nanotechnology and nanomaterials can alter and control neural functionality in both in vitro and in vivo experimental setups. The intersection between neuroscience and nanoscience may generate long-term neural interfaces adapted at the molecular level. Owing to their intrinsic physicochemical characteristics, gold nanostructures (GNSs) have received much attention in neuroscience, especially for combined diagnostic and therapeutic (theragnostic) purposes. GNSs have been successfully employed to stimulate and monitor neurophysiological signals. Hence, GNSs could provide a promising solution for the regeneration and recovery of neural tissue, novel neuroprotective strategies, and integrated implantable materials. This review covers the broad range of neurological applications of GNS-based materials to improve clinical diagnosis and therapy. Sub-topics include neurotoxicity, targeted delivery of therapeutics to the central nervous system (CNS), neurochemical sensing, neuromodulation, neuroimaging, neurotherapy, tissue engineering, and neural regeneration. It focuses on core concepts of GNSs in neurology, to circumvent the limitations and significant obstacles of innovative approaches in neurobiology and neurochemistry, including theragnostics. We will discuss recent advances in the use of GNSs to overcome current bottlenecks and tackle technical and conceptual challenges.

Surface enhanced fluorescence effect improves the in vivo detection of amyloid aggregates.

The ß-amyloid (Aß) peptide is one of the key etiological agents in Alzheimer's disease (AD). The in vivo detection of Aß species is challenging in all stages of the illness. Currently, the development of fluorescent probes allows the detection of Aß in animal models in the near-infrared region (NIR). However, considering future applications in biomedicine, it is relevant to develop strategies to improve detection of amyloid aggregates using NIR probes. An innovative approach to increase the fluorescence signal of these fluorophores is the use of plasmonic gold nanoparticles (surface-enhanced fluorescence effect). In this work, we improved the detection of Aß aggregates in C. elegans and mouse models of AD by co-administering functionalized gold nanorods (GNRs-PEG-D1) with the fluorescent probes CRANAD-2 or CRANAD-58, which bind selectively to different amyloid species (soluble and insoluble). This work shows that GNRs improve the detection of Aß using NIR probes in vivo.

Physicochemical and Theoretical Characterization of a New Small Non-Metal Schiff Base with a Differential Antimicrobial Effect against Gram-Positive Bacteria.

Searching for adequate and effective compounds displaying antimicrobial activities, especially against Gram-positive bacteria, is an important research area due to the high hospitalization and mortality rates of these bacterial infections in both the human and veterinary fields. In this work, we explored (E)-4-amino-3-((3,5-di-tert-butyl-2-hydroxybenzylidene)amino) benzoic acid (SB-1, harboring an intramolecular hydrogen bond) and (E)-2-((4-nitrobenzilidene)amino)aniline (SB-2), two Schiff bases derivatives. Results demonstrated that SB-1 showed an antibacterial activity determined by the minimal inhibitory concentration (MIC) against Staphylococcus aureus, Enterococcus faecalis, and Bacillus cereus (Gram-positive bacteria involved in human and animal diseases such as skin infections, pneumonia, diarrheal syndrome, and urinary tract infections, among others), which was similar to that shown by the classical antibiotic chloramphenicol. By contrast, this compound showed no effect against Gram-negative bacteria (Klebsiella pneumoniae, Escherichia coli, and Salmonella enterica). Furthermore, we provide a comprehensive physicochemical and theoretical characterization of SB-1 (as well as several analyses for SB-2), including elemental analysis, ESMS, 1H and 13C NMR (assigned by 1D and 2D techniques), DEPT, UV-Vis, FTIR, and cyclic voltammetry. We also performed a computational study through the DFT theory level, including geometry optimization, TD-DFT, NBO, and global and local reactivity analyses.

Gold nanoparticle based double-labeling of melanoma extracellular vesicles to determine the specificity of uptake by cells and preferential accumulation in small metastatic lung tumors.

BACKGROUND: Extracellular vesicles (EVs) have shown great potential for targeted therapy, as they have a natural ability to pass through biological barriers and, depending on their origin, can preferentially accumulate at defined sites, including tumors. Analyzing the potential of EVs to target specific cells remains challenging, considering the unspecific binding of lipophilic tracers to other proteins, the limitations of fluorescence for deep tissue imaging and the effect of external labeling strategies on their natural tropism. In this work, we determined the cell-type specific tropism of B16F10-EVs towards cancer cell and metastatic tumors by using fluorescence analysis and quantitative gold labeling measurements. Surface functionalization of plasmonic gold nanoparticles was used to promote indirect labeling of EVs without affecting size distribution, polydispersity, surface charge, protein markers, cell uptake or in vivo biodistribution. Double-labeled EVs with gold and fluorescent dyes were injected into animals developing metastatic lung nodules and analyzed by fluorescence/computer tomography imaging, quantitative neutron activation analysis and gold-enhanced optical microscopy. RESULTS: We determined that B16F10 cells preferentially take up their own EVs, when compared with colon adenocarcinoma, macrophage and kidney cell-derived EVs. In addition, we were able to detect the preferential accumulation of B16F10 EVs in small metastatic tumors located in lungs when compared with the rest of the organs, as well as their precise distribution between tumor vessels, alveolus and tumor nodules by histological analysis. Finally, we observed that tumor EVs can be used as effective vectors to increase gold nanoparticle delivery towards metastatic nodules. CONCLUSIONS: Our findings provide a valuable tool to study the distribution and interaction of EVs in mice and a novel strategy to improve the targeting of gold nanoparticles to cancer cells and metastatic nodules by using the natural properties of malignant EVs.

Encapsulation of Gold Nanostructures and Oil-in-Water Nanocarriers in Microgels with Biomedical Potential.

Here we report the incorporation of gold nanostructures (nanospheres or nanorods, functionalized with carboxylate-end PEG) and curcumin oil-in-water (O/W) nanoemulsions (CurNem) into alginate microgels using the dripping technique. While gold nanostructures are promising nanomaterials for photothermal therapy applications, CurNem possess important pharmacological activities as reported here. In this sense, we evaluated the effect of CurNem on cell viability of both cancerous and non-cancerous cell lines (AGS and HEK293T, respectively), demonstrating preferential toxicity in cancer cells and safety for the non-cancerous cells. After incorporating gold nanostructures and CurNem together into the microgels, microstructures with diameters of 220 and 540 µm were obtained. When stimulating microgels with a laser, the plasmon effect promoted a significant rise in the temperature of the medium; the temperature increase was higher for those containing gold nanorods (11⁻12 °C) than nanospheres (1⁻2 °C). Interestingly, the incorporation of both nanosystems in the microgels maintains the photothermal properties of the gold nanostructures unmodified and retains with high efficiency the curcumin nanocarriers. We conclude that these results will be of interest to design hydrogel formulations with therapeutic applications.

Peptide multifunctionalized gold nanorods decrease toxicity of ß-amyloid peptide in a Caenorhabditis elegans model of Alzheimer's disease.

The properties of nanometric materials make nanotechnology a promising platform for tackling problems of contemporary medicine. In this work, gold nanorods were synthetized and stabilized with polyethylene glycols and modified with two kinds of peptides. The D1 peptide that recognizes toxic aggregates of Aß, a peptide involved in Alzheimer's disease (AD); and the Angiopep 2 that can be used to deliver nanorods to the mammalian central nervous system. The nanoconjugates were characterized using absorption spectrophotometry, dynamic light scattering, and transmission electron microscopy, among other techniques. We determined that the nanoconjugate does not affect neuronal viability; it penetrates the cells, and decreases aggregation of Aß peptide in vitro. We also showed that when we apply our nanosystem to a Caenorhabditis elegans AD model, the toxicity of aggregated Aß peptide is decreased. This work may contribute to the development of therapies for AD based on metallic nanoparticles.

Conventional and new proposals of GnRH therapy for ovarian, breast, and prostatic cancers.

For many years, luteinizing hormone-releasing hormone or gonadotropin-releasing hormone (GnRH) analogs have been used to treat androgen or estrogen-dependent tumors. However, emerging evidence shows that the GnRH receptor (GnRH-R) is overexpressed in several cancer cells, including ovarian, endometrial, and prostate cancer cells, suggesting that GnRH analogs could exert direct antitumoral actions in tumoral tissues that express GnRH-R. Another recent approach based on this knowledge was the use of GnRH peptides for developing specific targeted therapies, improving the delivery and accumulation of drugs in tumoral cells, and decreasing most side effects of current treatments. In this review, we discuss the conventional uses of GnRH analogs, together with the recent advances in GnRH-based drug delivery for ovarian, breast, and prostatic cancer cells.

Differential Detection of Amyloid Aggregates in Old Animals Using Gold Nanorods by Computerized Tomography: A Pharmacokinetic and Bioaccumulation Study.

Introduction: The development of new materials and tools for radiology is key to the implementation of this diagnostic technique in clinics. In this work, we evaluated the differential accumulation of peptide-functionalized GNRs in a transgenic animal model (APPswe/PSENd1E9) of Alzheimer's disease (AD) by computed tomography (CT) and measured the pharmacokinetic parameters and bioaccumulation of the nanosystem. Methods: The GNRs were functionalized with two peptides, Ang2 and D1, which conferred on them the properties of crossing the blood-brain barrier and binding to amyloid aggregates, respectively, thus making them a diagnostic tool with great potential for AD. The nanosystem was administered intravenously in APPswe/PSEN1dE9 model mice of 4-, 8- and 18-months of age, and the accumulation of gold nanoparticles was observed by computed tomography (CT). The gold accumulation and biodistribution were determined by atomic absorption. Results: Our findings indicated that 18-month-old animals treated with our nanosystem (GNR-D1/Ang2) displayed noticeable differences in CT signals compared to those treated with a control nanosystem (GNR-Ang2). However, no such distinctions were observed in younger animals. This suggests that our nanosystem holds the potential to effectively detect AD pathology. Discussion: These results support the future development of gold nanoparticle-based technology as a more effective and accessible alternative for the diagnosis of AD and represent a significant advance in the development of gold nanoparticle applications in disease diagnosis.

Peptide Targeted Gold Nanoplatform Carrying miR-145 Induces Antitumoral Effects in Ovarian Cancer Cells.

One of the recent attractive therapeutic approaches for cancer treatment is restoring downregulated microRNAs. They play an essential muti-regulatory role in cellular processes such as proliferation, differentiation, survival, apoptosis, cell cycle, angiogenesis, and metastasis, among others. In this study, a gold nanoplatform (GNPF) carrying miR-145, a downregulated microRNA in many cancer types, including epithelial ovarian cancer, was designed and synthesized. For targeting purposes, the GNPF was functionalized with the FSH33 peptide, which provided selectivity for ovarian cancer, and loaded with the miR-145 to obtain the nanosystem GNPF-miR-145. The GNPF-mir-145 was selectively incorporated in A2780 and SKOV3 cells and significantly inhibited cell viability and migration and exhibited proliferative and anchor-independent growth capacities. Moreover, it diminished VEGF release and reduced the spheroid size of ovarian cancer through the damage of cell membranes, thus decreasing cell viability and possibly activating apoptosis. These results provide important advances in developing miR-based therapies using nanoparticles as selective vectors and provide approaches for in vivo evaluation.

Oligoarginine Peptide Conjugated to BSA Improves Cell Penetration of Gold Nanorods and Nanoprisms for Biomedical Applications.

Gold nanoparticles (AuNPs) have been shown to be outstanding tools for drug delivery and biomedical applications, mainly owing to their colloidal stability, surface chemistry, and photothermal properties. The biocompatibility and stability of nanoparticles can be improved by capping the nanoparticles with endogenous proteins, such as albumin. Notably, protein coating of nanoparticles can interfere with and decrease their cell penetration. Therefore, in the present study, we functionalized albumin with the r8 peptide (All-D, octaarginine) and used it for coating NIR-plasmonic anisotropic gold nanoparticles. Gold nanoprisms (AuNPrs) and gold nanorods (AuNRs) were coated with bovine serum albumin (BSA) previously functionalized using a cell penetrating peptide (CPP) with the r8 sequence (BSA-r8). The effect of the coated and r8-functionalized AuNPs on HeLa cell viability was assessed by the MTS assay, showing a low effect on cell viability after BSA coating. Moreover, the internalization of the nanostructures into HeLa cells was assessed by confocal microscopy and transmission electron microscopy (TEM). As a result, both nanoconstructs showed an improved internalization level after being capped with BSA-r8, in contrast to the BSA-functionalized control, suggesting the predominant role of CPP functionalization in cell internalization. Thus, our results validate both novel nanoconstructs as potential candidates to be coated by endogenous proteins and functionalized with a CPP to optimize cell internalization. In a further approach, coating AuNPs with CPP-functionalized BSA can broaden the possibilities for biomedical applications by combining their optical properties, biocompatibility, and cell-penetration abilities.

The Influence of Size and Chemical Composition of Silver and Gold Nanoparticles on in vivo Toxicity with Potential Applications to Central Nervous System Diseases.

The physicochemical and optical properties of silver nanoparticles (SNPs) and gold nanoparticles (GNPs) have allowed them to be employed for various biomedical applications, including delivery, therapy, imaging, and as theranostic agents. However, since they are foreign body systems, they are usually redistributed and accumulated in some vital organs, which can produce toxic effects; therefore, this a crucial issue that should be considered for potential clinical trials. This review aimed to summarize the reports from the past ten years that have used SNPs and GNPs for in vivo studies on the diagnosis and treatment of brain diseases and those related to the central nervous system, emphasizing their toxicity as a crucial topic address. The article focuses on the effect of the nanoparticle´s size and chemical composition as relevant parameters for in vivo toxicity. At the beginning of this review, the general toxicity and distribution studies are discussed separately for SNPs and GNPs. Subsequently, this manuscript analyzes the principal applications of both kinds of nanoparticles for glioma, neurodegenerative, and other brain diseases, and discusses the advances in clinical trials. Finally, we analyze research prospects towards clinical applications for both types of metallic nanoparticles.

Functionalization with PEG/Angiopep-2 peptide to improve the delivery of gold nanoprisms to central nervous system: in vitro and in vivo studies.

One of main drawbacks for the treatment of neurodegenerative pathologies is ensuring the delivery of therapeutic agents into the central nervous system (CNS). Nowadays, gold nanoprisms (GNPr) have become an emerging nanomaterial with a localized surface plasmon resonance in the biological window, showing applications in both detection and treatment of diseases. In this work, GNPr were functionalized with polyethylene glycol (PEG) and Angiopep-2 (Ang2) peptide to obtain a new highly stable nanomaterial and evaluate its toxicity and ability to cross the blood-brain barrier (BBB) in a zebrafish larvae model. The success in the functionalization was confirmed by a full characterization that showed the physicochemical changes at each step. In turn, the colloidal stability of GNPr-PEG-Ang2 in biologically relevant media also was demonstrated. The toxicity assays of GNPr-PEG-Ang2 performed on SH-SY5Y neuroblastoma cell line and on zebrafish larvae showed no effects both in vitro and in vivo. GNPr delivery to the CNS was studied in zebrafish larvae by immersion. We confirmed that functionalization with PEG-Ang2 improved the crossing through the BBB in this model compared with GNPr functionalized only with PEG. Notably, our nanomaterial was not detected in the CNS of zebrafish larvae 24 h after exposure that correlates with an adequate clearance of GNPr-PEG-Ang2 from the brain. This report is the first study of GNPr in the in vivo model of zebrafish larvae demonstrating that its functionalization with Ang2 allows the crossing of the BBB. Moreover, considering the stability achieved of the GNPr-PEG-Ang2 and the results of in vitro and in vivo studies, this work becomes a high contribution to the design of new nanomaterials with potential biomedical applications for CNS-related diseases.

NIR and glutathione trigger the surface release of methotrexate linked by Diels-Alder adducts to anisotropic gold nanoparticles.

The administration and controlled release of drugs over time remains one of the greatest challenges of science today. In the nanomaterials field, anisotropic gold nanoparticles (AuNPs) with plasmon bands centered at the near-infrared region (NIR), such as gold nanorods (AuNRs) and gold nanoprisms (AuNPrs), under laser irradiation, locally increase the temperature, allowing the release of drugs. In this sense, temporally controlled drug delivery could be promoted by external stimuli using thermo-reversible chemical reactions, such as Diels-Alder cycloadditions from a diene and a dienophile fragment (compound a). In this study, an antitumor drug (methotrexate, MTX) was linked to plasmonic AuNPs by a Diels-Alder adduct (compound c), which after NIR suffers a retro-Diels-Alder reaction, producing release of the drug (compound b). We obtained two nanosystems based on AuNRs and AuNPrs. Both nanoconstructs were coated with BSA-r8 (Bovine Serum Albumin functionalized with Arg8, all-D octa arginine) in order to increase the colloidal stability and promote internalization of the nanosystems on HeLa and SK-BR-3 cells. In addition, the presence of BSA allows protecting the cargo from being released on the extracellular environment and promotes the photothermal release of the drug in the presence of glutathione (GSH). The nanosystems' drug release profile was evaluated after NIR irradiation in the presence and absence of glutathione (GSH), showing a considerable increase of drug release when NIR light and glutathione were combined. This work broadens the range of possibilities of using two complementary strategies for the controlled release of an antitumor drug from AuNRs and AuNPrs: the photothermal cleavage of a thermolabile adduct controlled by an external stimulus (laser irradiation), complemented with the use of the intracellular metabolite GSH.

"One for All": Functional Transfer of OMV-Mediated Polymyxin B Resistance From Salmonella enterica sv. Typhi ΔtolR and ΔdegS to Susceptible Bacteria.

The appearance of multi-resistant strains has contributed to reintroducing polymyxin as the last-line therapy. Although polymyxin resistance is based on bacterial envelope changes, other resistance mechanisms are being reported. Outer membrane vesicles (OMVs) are nanosized proteoliposomes secreted from the outer membrane of Gram-negative bacteria. In some bacteria, OMVs have shown to provide resistance to diverse antimicrobial agents either by sequestering and/or expelling the harmful agent from the bacterial envelope. Nevertheless, the participation of OMVs in polymyxin resistance has not yet been explored in S. Typhi, and neither OMVs derived from hypervesiculating mutants. In this work, we explored whether OMVs produced by the hypervesiculating strains Salmonella Typhi ΔrfaE (LPS synthesis), ΔtolR (bacterial envelope) and ΔdegS (misfolded proteins and σ E activation) exhibit protective properties against polymyxin B. We found that the OMVs extracted from S. Typhi ΔtolR and ΔdegS protect S. Typhi WT from polymyxin B in a concentration-depending manner. By contrast, the protective effect exerted by OMVs from S. Typhi WT and S. Typhi ΔrfaE is much lower. This effect is achieved by the sequestration of polymyxin B, as assessed by the more positive Zeta potential of OMVs with polymyxin B and the diminished antibiotic's availability when coincubated with OMVs. We also found that S. Typhi ΔtolR exhibited an increased MIC of polymyxin B. Finally, we determined that S. Typhi ΔtolR and S. Typhi ΔdegS, at a lesser level, can functionally and transiently transfer the OMV-mediated polymyxin B resistance to susceptible bacteria in cocultures. This work shows that mutants in genes related to OMVs biogenesis can release vesicles with improved abilities to protect bacteria against membrane-active agents. Since mutations affecting OMV biogenesis can involve the bacterial envelope, mutants with increased resistance to membrane-acting agents that, in turn, produce protective OMVs with a high vesiculation rate (e.g., S. Typhi ΔtolR) can arise. Such mutants can functionally transfer the resistance to surrounding bacteria via OMVs, diminishing the effective concentration of the antimicrobial agent and potentially favoring the selection of spontaneous resistant strains in the environment. This phenomenon might be considered the source for the emergence of polymyxin resistance in an entire bacterial community.

Study of the interaction of folic acid-modified gold nanorods and fibrinogen through microfluidics: implications for protein adsorption, incorporation and viability of cancer cells.

Gold nanoparticles (GNPs) are an attractive nanomaterial for potential applications in therapy and diagnostics due to their capability to direct toward specific sites in the organism. However, when exposed to plasma, GNPs can interact with different biomolecules that form a dynamic nano-bio interface called a "protein corona" (PC). Remarkably, the PC could affect multiple biological processes, such as cell targeting and uptake, cytotoxicity, and nanoparticle (NP) clearance. The interaction of nanomaterials with plasmatic proteins has been widely studied under bulk conditions, however, under dynamic conditions, it has just recently been explored. Thus, to mimic a dynamic natural environment found in arteries and veins, microfluidic devices were used. In this work, gold nanorods (GNRs) were synthesized and conjugated with polyethylene glycol (PEG) to reduce their interaction with plasma proteins and increase their biocompatibility. Then, GNRs were functionalized with folic acid, a targeting ligand typically used to recognize tumor cells. The resulting nanosystem was exposed to fibrinogen (FB) to study the development and biological impact of PC formation through two strategies: bulk and laminar flow conditions. The obtained nanosystems were characterized by absorption spectrophotometry, DLS, laser Doppler microelectrophoresis, neutron activation analysis, circular dichroism spectroscopy and TEM. Finally, cell viability and cellular uptake assays were performed to study the influence of the PC on the cell viability and delivery of nanosystems.

In vivo micro computed tomography detection and decrease in amyloid load by using multifunctionalized gold nanorods: a neurotheranostic platform for Alzheimer's disease.

The development and use of nanosystems is an emerging strategy for the diagnosis and treatment of a broad number of diseases, such as Alzheimer's disease (AD). Here, we developed a neurotheranostic nanosystem based on gold nanorods (GNRs) that works as a therapeutic peptide delivery system and can be detected in vivo for microcomputed tomography (micro-CT), being a diagnostic tool. GNRs functionalized with the peptides Ang2 (a shuttle to the Central Nervous System) and D1 (that binds to the Aß peptide, also inhibiting its aggregation) allowed detecting differences in vivo between wild type and AD mice (APPswe/PSEN1dE9) 15 minutes after a single dose by micro-CT. Moreover, after a recurrent treatment for one month with GNRs-D1/Ang2, we observed a diminution of amyloid load and inflammatory markers in the brain. Thus, this new designed nanosystem exhibits promising properties for neurotheranostics of AD.

Adsorption of bovine serum albumin on gold nanoprisms: interaction and effect of NIR irradiation on protein corona.

Because of their photothermal properties, gold nanoparticles (AuNPs) have gained attention regarding their use in drug delivery and therapeutic applications. In this sense, it is interesting to consider their interactions with biologically available proteins, such as serum albumin, as well as the effects of irradiation and photothermal conversion on the protein structure that can lead to a loss of function or generate an immune response. Gold nanoprisms (AuNPrs) have gained interest due to their low toxicity, ease of synthesis, and excellent stability, promoting their use in bioapplications such as surface-enhanced Raman spectroscopy (SERS), drug delivery, and photothermal therapy. The interaction between AuNPrs, with plasmon bands centred in the near-infrared region (NIR), and bovine serum albumin (BSA) has not been explored yet. UV-Vis spectroscopy, dynamic light scattering (DLS) and fluorescence spectroscopy were used to study the interaction between AuNPrs and BSA in addition to estimation of the adsorption rate and kinetic and thermodynamic parameters (K, ΔH°, ΔG°, ΔS°, and Ea) using adsorption isotherms and Langmuir and Freundlich models. The results suggest spontaneous cooperative binding in multilayer adsorption, achieved by the chemisorption of BSA on the AuNPr surface through the S-Au interaction, as confirmed by Raman spectroscopy. On the other hand, the photothermal conversion efficiency (PE) of the coated nanoparticles after NIR irradiation was assessed, resulting in a slight decrease in the PE of BSA coated on AuNPrs in comparison with that of noncapped nanoparticles. The effect of the irradiation on the protein conformation of capped nanoparticles was also assessed; circular dichroism showed BSA unfolding upon interaction with AuNPrs, with a decrease in the α-helix and ß-sheet contents, as well as an increase in random coil conformations. Changes in the Raman spectrum suggest a modification of the disposition of the protein residues exposed to the gold surface after NIR irradiation; but at the secondary structure level, no relevant changes were observed. This provides possibilities for the use of NPs-BSA for bioapplications based on the photothermal effect promoted by laser irradiation, since the biological identity of the protein is preserved after NIR irradiation.

Improving Cell Penetration of Gold Nanorods by Using an Amphipathic Arginine Rich Peptide.

INTRODUCTION: Gold nanorods are highly reactive, have a large surface-to-volume ratio, and can be functionalized with biomolecules. Gold nanorods can absorb infrared electromagnetic radiation, which is subsequently dispersed as local heat. Gold nanoparticles can be used as powerful tools for the diagnosis and therapy of different diseases. To improve the biological barrier permeation of nanoparticles with low cytotoxicity, in this study, we conjugated gold nanorods with cell-penetrating peptides (oligoarginines) and with the amphipathic peptide CLPFFD. METHODS: We studied the interaction of the functionalized gold nanorods with biological membrane models (liposomes) by dynamic light scattering, transmission electron microscopy and the Langmuir balance. Furthermore, we evaluated the effects on cell viability and permeability with an MTS assay and TEM. RESULTS AND DISCUSSION: The interaction study by DLS, the Langmuir balance and cryo-TEM support that GNR-Arg7CLPFFD enhances the interactions between GNRs and biological membranes. In addition, cells treated with GNR-Arg7CLPFFD internalized 80% more nanoparticles than cells treated with GNR alone and did not induce cell damage. CONCLUSION: Our results indicate that incorporation of an amphipathic sequence into oligoarginines for the functionalization of gold nanorods enhances biological membrane nanoparticle interactions and nanoparticle cell permeability with respect to nanorods functionalized with oligoarginine. Overall, functionalized gold nanorods with amphipathic arginine rich peptides might be candidates for improving drug delivery by facilitating biological barrier permeation.

Light-induced release of the cardioprotective peptide angiotensin-(1-9) from thermosensitive liposomes with gold nanoclusters.

Angiotensin-(1-9), a component of the non-canonical renin-angiotensin system, has a short half-life in blood. This peptide has shown to prevent and/or attenuate hypertension and cardiovascular remodeling. A controlled release of angiotensin-(1-9) is needed for its delivery to the heart. Our aim was to develop a drug delivery system for angiotensin-(1-9). Thermosensitive liposomes (LipoTherm) were prepared with gold nanoclusters (LipoTherm-AuNC) to increase the stability and reach a temporal and spatial control of angiotensin-(1-9) release. Encapsulation efficiencies of nearly 50% were achieved in LipoTherm, reaching a total angiotensin-(1-9) loading of around 180 µM. This angiotensin-(1-9)-loaded LipoTherm sized around 100 nm and exhibited a phase transition temperature of 43 °C. AuNC were grown on LipoTherm and the new hybrid nanosystem showed energy absorption in the near-infrared (NIR) wavelength range. By NIR laser irradiation, a controlled release of angiotensin-(1-9) was achieved from the LipoTherm-AuNC nanosystem. These nanosystems did not show any cytotoxic effect on cultured cardiomyocytes. Biological activity of angiotensin-(1-9) released from the LipoTherm-AuNC-based nanosystem was confirmed using an ex vivo Langendorff heart model.

Capping gold nanoparticles with albumin to improve their biomedical properties.

Nanotechnology is an emerging field which has created great opportunities either through the creation of new materials or by improving the properties of existing ones. Nanoscale materials with a wide range of applications in areas ranging from engineering to biomedicine have been produced. Gold nanoparticles (AuNPs) have emerged as a therapeutic agent, and are useful for imaging, drug delivery, and photodynamic and photothermal therapy. AuNPs have the advantage of ease of functionalization with therapeutic agents through covalent and ionic binding. Combining AuNPs and other materials can result in nanoplatforms, which can be useful for biomedical applications. Biomaterials such as biomolecules, polymers and proteins can improve the therapeutic properties of nanoparticles, such as their biocompatibility, biodistribution, stability and half-life. Serum albumin is a versatile, non-toxic, stable, and biodegradable protein, in which structural domains and functional groups allow the binding and capping of inorganic nanoparticles. AuNPs coated with albumin have improved properties such as greater compatibility, bioavailability, longer circulation times, lower toxicity, and selective bioaccumulation. In the current article, we review the features of albumin, as well as its interaction with AuNPs, focusing on its biomedical applications.