Peptidic nanoparticles: for cancer diagnosis and therapy

A challenging topic in cancer research is to create drug delivery system that can bring in a specific and noncytotoxic manner a therapeutic compound. Usually, tumor targeting requires very specific compounds. Currently, peptide analogues like somatostatin, neurotensin, or bombesin are used to target G-coupled receptors, which are overexpressed on tumor cells. However, many of those analogues are rapidly degraded in the plasma and are cytotoxic [1–2]. Due to the limited efficiency and high toxicity of conventional chemotherapy different strategies have been developed for non-cytotoxic cancer treatment and cancer localization [3–5]. The recent development in bio-nanotechnology offers new avenues for cancer therapy. A lot of studies have been devoted to nanoparticulate delivery systems (10–100nm) like lipid or polymer particles [6–8]. Due to the nanometer sized of such cargos, the transportation of therapeutic compounds in the blood stream is increased in terms of time circulation. But their surface functionalization to improve drug-targeting properties is usually complicated and rather uneffective. We have recently designed a novel type of functional nanoparticles with regular icosahedral symmetry, mimicking small, rigid viral capsids (Fig. 1 (A)) and a diameter of about 17 nm (Fig. 1 (C)) which self-assemble from single polypeptide chains (Fig. 1 (B)).     

Lanthanum biosorption by a Pseudomonas sp.: equilibrium studies and chemical characterization

Lanthanum biosorption by a Pseudomonas sp. was characterized in terms of equilibrium metal loading, model fitting, kinetics, effect of solution pH, lanthanum–bacteria interaction mechanism and recovery of sorbed metal. Lanthanum sorption by the bacterium was rapid and optimum at pH 5.0 with equilibrium metal loading as high as 950 mg g⁻¹ biomass dry wt. Scatchard model and potentiometric titration suggested the presence of at least two types of metal-binding sites, corresponding to a strong and a weak binding affinity. The chemical nature of metal–microbe interaction has been elucidated employing FTIR spectroscopy, energy dispersive X-ray analysis (EDX) and X-ray diffraction analysis (XRD). FTIR spectroscopy and XRD analysis revealed strong involvement of cellular carboxyl and phosphate groups in lanthanum binding by the bacterial biomass. EDX and the elemental analysis of the sorption solution ascertained the binding of lanthanum with the bacterial biomass via displacement of cellular potassium and calcium. Transmission electron microscopy exhibited La accumulation throughout the bacterial cell with some granular deposits in cell periphery and in cytoplasm. XRD confirmed the presence of LaPO₄ crystals onto the bacterial biomass after La accumulation for a long period. A combined ion-exchange–complexation–microprecipitation mechanism could be involved in lanthanum accumulation by the biomass. Almost 98% of biomass-bound La could be recovered using CaCO₃ as the desorbing agent.     

Role of C-reactive protein in complement-mediated hemolysis in Malaria

Human C-reactive protein (CRP) is a clinically important classical acute phase protein. Although CRP has been reported to bind with many nucleated cells, the direct binding of CRP to erythrocytes in diseases remains largely unexplored. The main focus of the present study was to investigate the binding of disease-specific CRP to erythrocytes of same patients. Distinct molecular variant of disease-specific CRP was affinity purified from sera of malaria patients (CRP_Mal). This CRP showed strong binding with malaria erythrocytes (RBC_Mal) as confirmed by flow cytometric analysis (FACS), enzyme-linked immunosorbent assays (ELISA), and radio binding assays. Calcium and phosphoryl choline (PC) were found to be essential for this interaction. A 2.3-fold increased binding of induced CRP to RBC_Mal as compared to normal erythrocytes (RBC_N) confirmed disease-specificity. Preincubation of RBC_Mal with unconjugated CRP showed 3–5 fold inhibition. The association constant of CRP and RBC_Mal was 4.7 × 10⁶ cpm/μg with the corresponding number of receptors/cell being 4.3 × 10⁵. The effector function of CRP_Mal has been demonstrated by its potency to activate the complement pathway. An optimal dose of 10 μg/ml of CRP induced three-fold higher hemolysis of patient erythrocytes as compared to RBC_N. These studies provide direct evidence for an important phagocytic functional interaction of this acute-phase protein by triggering the CRP-complement pathway after the binding of CRP_Mal with RBC_Mal. Hemolysis as triggered by this pathway may be one of the causative factors of anemia, a common clinical manifestation of this disease.