Ariel R. Guerrero

Peptides and metallic nanoparticles for biomedical applications

In this review, we describe the contribution of peptides to the biomedical applications of metallic nanoparticles. We also discuss strategies for the preparation of peptide-nanoparticle conjugates and the synthesis of the peptides and metallic nanoparticles. An overview of the techniques used for the characterization of the conjugates is also provided. Mainly for biomedical purposes, metallic nanoparticles conjugated to peptides have been prepared from Au and iron oxide (magnetic nanoparticles). Peptides with the capacity to penetrate the plasma membrane are used to deliver nanoparticles to the cell. In addition, peptides that recognize specific cell receptors are used for targeting nanoparticles. The potential application of peptide-nanoparticle conjugates in cancer and Alzheimers disease therapy is discussed. Several peptide-nanoparticle conjugates show biocompatibility and present a low degree of cytotoxicity. Furthermore, several peptide-metallic nanoparticle conjugates are used for in vitro diagnosis.

Gold nanoparticles for photothermally controlled drug release

In this article, we describe how nanoparticles work in photothermally triggered drug delivery, starting with a description of the plasmon resonance and the photothermal effect, and how this is used to release a drug. Then, we describe the four major functionalization strategies and each of their different applications. Finally, we discuss the biodistribution and toxicity of these systems and the necessary requirements for the use of gold nanoparticles for spatially and temporally controlling drug release through the photothermal effect.

Exploring the Surface Charge on Peptide−Gold Nanoparticle Conjugates by Force Spectroscopy

The conformation and charge exposure of peptides attached to colloidal gold nanoparticles (AuNPs) are critical for both the colloidal stability and for the recognition of biological targets in biomedical applications such as diagnostics and therapy. We prepared conjugates of AuNPs and three isomer peptides capable of recognizing toxic aggregates of the amyloid beta protein (Abeta) involved in Alzheimers disease, namely, CLPFFD-CONH(2) (i0), CDLPFF-CONH(2) (i1), and CLPDFF-CONH(2) (i2), where D is the amino acid aspartic acid that is negatively charged at pH = 7.4. We then studied the effect of peptide sequence on the charge exposure through force spectroscopy measurements. The peptide-AuNPs conjugates were fixed on glass surfaces, and their interactions with peptide-functionalized tips were determined. Our results show a higher density of surface charge in the conjugates of the isomers i0 and i2 and a lower density in i1, which is due to the higher degree of functionalization in the first two compared with the third. However, the charge per molecule of the peptide is higher for i1 with respect to i0 and i2, which could be related to the local conformation that the peptides adopt on the surface. The acid-base behavior of the peptide anchored to the AuNPs is different than expected in aqueous solutions of free peptides, which could be related to the low accessibility of the NH(2)-terminal group belonging to the cysteine that is located near the AuNPs surface. In contrast with other techniques, the fixation of the peptide-AuNPs conjugates to a surface allows for characterization of the local charge exposure of peptides anchored to AuNPs over a wide range of pH.

Gold Nanoparticles Interacting with β-Cyclodextrin–Phenylethylamine Inclusion Complex: A Ternary System for Photothermal Drug Release

We report the synthesis of a 1:1 β-cyclodextrin-phenylethylamine (βCD-PhEA) inclusion complex (IC) and the adhesion of gold nanoparticles (AuNPs) onto microcrystals of this complex, which forms a ternary system. The formation of the IC was confirmed by powder X-ray diffraction and NMR analyses ((1)H and ROESY). The stability constant of the IC (760 M(-1)) was determined using the phase solubility method. The adhesion of AuNPs was obtained using the magnetron sputtering technique, and the presence of AuNPs was confirmed using UV-vis spectroscopy (surface plasmon resonance effect), which showed an absorbance at 533 nm. The powder X-ray diffractograms of βCD-PhEA were similar to those of the crystals decorated with AuNPs. A comparison of the one- and two-dimensional NMR spectra of the IC with and without AuNPs suggests partial displacement of the guest to the outside of the βCD due to attraction toward AuNPs, a characteristic tropism effect. The size, morphology, and distribution of the AuNPs were analyzed using TEM and SEM. The average size of the AuNPs was 14 nm. Changes in the IR and Raman spectra were attributed to the formation of the complex and to the specific interactions of this group with the AuNPs. Laser irradiation assays show that the ternary system βCD-PhEA-AuNPs in solution enables the release of the guest.

Organic and Inorganic Nanoparticles for Prevention and Diagnosis of Gastric Cancer.

Organic and inorganic nanoparticles show great potential for cancer diagnosis and treatment. Because gastric cancer (GC) represents the second most deadly type of neoplasia worldwide, continued research efforts by scientists and clinicians are essential to improve diagnosis and treatment. This paper reviews significant findings in the area of nanoparticles (organic and inorganic origin) that may aid in prevention and diagnosis of GC. This review focuses in the first section on H. pylori and the connection to GC, highlighting nanoformulations designed to control bacterial growth. The second section evaluates the potential of different imaging techniques (especially using inorganic nanoparticles) in the detection of GC, and the third section summarizes how nanotechnology may be employed in the analytical detection of GC biomarkers (metallic plasmons, electrochemical biosensors and colorimetric sensors). We foresee that the prevention and diagnosis of GC will require the development of complex collaborative studies. Additionally, scientists also need to be tightly connected to industry in order to facilitate upscaling and rapid transfer of promising products to the clinic.

The case for aflatoxins in the causal chain of gallbladder cancer

Chronic aflatoxin exposure has long been related to hepatocellular carcinoma (HCC). Recently, its association with gallbladder cancer (GBC) was postulated. Here we present the data supporting this hypothesis in Chile, the country with the highest GBC mortality worldwide with age-standardized mortality rates (ASMR) of 10.3 in women and 5.04 in men. The highest GBC rates occur in Southern Chile (ASMR=18), characterized by: high Amerindian ancestry, associated with high bile acid synthesis and gallstones; high poverty and high cereal agriculture, both associated with aflatoxin exposure. Aflatoxins have been detected in imported and locally grown foods items. We estimated population dietary exposure ranging from 0.25 to 35.0 ng/kg-body weight/day. The only report on human exposure in Chile found significantly more aflatoxin biomarkers in GBC than in controls (Odds Ratio=13.0). The hypothesis of aflatoxin-GBC causal link in the Chilean population is supported by: genetically-determined rapid cholesterol excretion and high gallstones prevalence (49.4%); low prevalence of HCC (ASMR=4.9) and low HBV infection (0.15%) the main co-factor of aflatoxins in HCC risk. If the association between aflatoxins and GBC were confirmed, public health interventions based on food regulation could have a substantial public health impact.

Gastric Cancer: Nanoparticles as Tools to Improve Treatment Efficacy

In recent years, advances in nanotechnology have raised the specter of developing effective agents for the treatment of high-impact diseases, like gastric cancer, which remains one of the major causes of cancer deaths worldwide. This article reviews advances in the treatment of this pathology using several types of nanoparticles. First, we start with an overview of gastric cancer, its prevention, detection and the available treatments. Then, we discuss nanotechnology-based novel strategies using polymeric nanosystems, nanovesicular systems and inorganic nanoparticles. All of these systems are being evaluated in the perspective of improving the targeting of anticancer drugs and reducing their negative side effects.