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Intrinsic functional and architectonic heterogeneity of tumor-targeted protein nanoparticles

Abstract

Self-assembling proteins are gaining interest as building blocks of application-tailored nanoscale materials. This is mostly due to biocompatibility, biodegradability, and functional versatility of peptide chains. Such potential for adaptability is particularly high in the case of recombinant proteins, which produced in living cells are suited for genetic engineering. However, how the cell factory itself and the particular protein folding machinery influence architecture and function of the final material is still poorly explored. In this study we have used diverse analytic approaches, including small-angle X-ray scattering (SAXS) and field emission scanning electron microscopy (FESEM) to determine the fine architecture and geometry of recombinant, tumor-targeted protein nanoparticles of interest as drug carriers, constructed on a GFP-based modular scheme. A set of related oligomers were produced in alternative Escherichia coli strains with variant protein folding networks. This resulted into highly regular populations of morphometric types, ranging from 2.4 to 28 nm and from spherical to rod-shaped materials. These differential geometric species, whose relative proportions were determined by features of the producing strain, were found associated to particular fluorescence emission, cell penetrability and receptor specificity profiles. Then, nanoparticles with optimal properties could be analytically identified and further isolated from producing cells for use. The cell’s protein folding machinery greatly modulates the final geometry reached by the constructs, which in turn defines key parameters and biological performance of the material.

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Publication details

The article was received on 25 Nov 2016, accepted on 09 Apr 2017 and first published on 10 Apr 2017


Article type: Paper
DOI: 10.1039/C6NR09182B
Citation: Nanoscale, 2017, Accepted Manuscript
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    Intrinsic functional and architectonic heterogeneity of tumor-targeted protein nanoparticles

    M. Pesarrodona, E. Crosas, R. Cubarsi, A. Sanchez-Chardi, P. Saccardo, U. Unzueta, F. Rueda, L. Sánchez-García, N. Serna, R. Mangues, N. Ferrer-Miralles, E. Vazquez and A. Villaverde, Nanoscale, 2017, Accepted Manuscript , DOI: 10.1039/C6NR09182B

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