Carbon nanohorns functionalized with polyamidoamine dendrimers as efficient biocarrier materials for gene therapy

[EN] Carbon nanohorns are suitable platforms for use in biological applications. Their high surface areas allow the incorporation of molecular entities, such as polyamidoamine dendrimers. In this work, we report the synthesis, structural characterization and biological data of new hybrid systems of carbon nanohorns that hold polyamidoamine dendrimers. One of these derivatives has been employed as an agent for gene delivery. The system is able to release interfering genetic material diminishing the levels of a house-keeping protein and a protein directly involved in prostate cancer development. Importantly, this hybrid material is also far less toxic than the corresponding free dendrimer. These results allow us to conclude that these nanomaterials can be exploited as useful non-viral agents for gene therapy.M.A.H., N.R., M.L. and E.V. are grateful to DGICYT of Spain for funding through the Project CTQ2007-60037/BQU and to Consejeria de Educacion y Ciencia (JCCM) for funding projects PBI-06-0020 and PCI08-0040. J.G. also acknowledges the Ministerio de Ciencia e Innovacion (MICINN) (Spain) (BFU2011-30161-C02-02), MICINN (Spain)-Fondo Europeo de Desarrollo Regional (FEDER, European Union) (Project CTQ2006-08871) and JCCM (Project PCI08-0033). This work has been supported, in part, by Grants PI081434 from Fondo de Investigaciones Sanitarias, BFU2011-30161-C02-01 from MICINN and PII1109-0163-4002 and POII10-0274-3182 from Consejeria de Educacion, JCCM to V.C. J.G., F.C.P.-M and B.C. are recipients of Torres-Quevedo research contracts funded by MICINN (Spain) and Nano-Drugs S.L. Authors are very grateful to Dr. V. Sue Myers at UT-Austin and Claudio Gamboz of Settore Microscopia Elettronica at University of Trieste for their help with the TEM measurements. We also thank Ana Belen Garcia for her expert technical assistance. Authors are also very grateful to Dr. Sonia Merino and Dr. Prado Sanchez-Verdti for fruitful discussions.Guerra, J.; Herrero, MA.; Carrión, B.; Pérez-Martínez, FC.; Lucío, MI.; Rubio, N.; Meneghetti, M.... (2012). Carbon nanohorns functionalized with polyamidoamine dendrimers as efficient biocarrier materials for gene therapy. Carbon. 50(8):2832-2844. https://doi.org/10.1016/j.carbon.2012.02.0502832284450

The nanomechanics of neurotoxina proteins reveals common features at the start of the neurodegeneration cascade.

1 pags. -- 56th Annual Meeting of the Biophysical-Society, FEB 25-29, 2012, San Diego, CAAmyloidogenic neurodegenerative diseases are incurable conditions caused by specific largely disordered proteins. However, the underlying molecular mechanism remains elusive. A favored hypothesis postulates that a critical conformational change in the monomer (an ideal therapeutic target) in these ‘‘neurotoxic proteins’’ triggers the pathogenic cascade. Using force spectroscopy with unequivocal singlemolecule identification we demonstrate a rich conformational polymorphism at their monomer level. This polymorphism strongly correlates with amyloidogenesis and neurotoxicity: it is absent in a fibrillization-incompetent mutant, favored by familial-disease mutations and diminished by a surprisingly promiscuous inhibitor of the monomeric b-conformational change and neurodegeneration. The demonstrated ability to inhibit the conformational heterogeneity of these proteins by a single pharmacological agent reveals common features in the monomer and suggests a common pathway to diagnose, prevent, halt or reverse multiple neurodegenerative disease

Modelling the unfolding pathway of biomolecules: theoretical approach and experimental prospect

We analyse the unfolding pathway of biomolecules comprising several independent modules in pulling experiments. In a recently proposed model, a critical velocity $v_{c}$ has been predicted, such that for pulling speeds $v>v_{c}$ it is the module at the pulled end that opens first, whereas for $v<v_{c}$ it is the weakest. Here, we introduce a variant of the model that is closer to the experimental setup, and discuss the robustness of the emergence of the critical velocity and of its dependence on the model parameters. We also propose a possible experiment to test the theoretical predictions of the model, which seems feasible with state-of-art molecular engineering techniques.Comment: Accepted contribution for the Springer Book "Coupled Mathematical Models for Physical and Biological Nanoscale Systems and Their Applications" (proceedings of the BIRS CMM16 Workshop held in Banff, Canada, August 2016), 16 pages, 6 figure

Common Features at the Start of the Neurodegeneration Cascade

A single-molecule study reveals that neurotoxic proteins share common structural features that may trigger neurodegeneration, thus identifying new targets for therapy and diagnosis