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Nanoscale. 2017 May 18;9(19):6427-6435. doi: 10.1039/c6nr09182b.

Intrinsic functional and architectonic heterogeneity of tumor-targeted protein nanoparticles.

Author information

1
Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Spain. Esther.Vazquez@uab.cat antoni.villaverde@uab.es and Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Spain and CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Spain.
2
ALBA Synchrotron, Carrer de la llum, 2-26, 08290 Cerdanyola del Vallès, Spain.
3
Department of Mathematics, Campus Diagonal Sud, Edifici U, Universitat Politècnica de Catalunya, Carrer de Pau Gargallo, 5, 08028 Barcelona, Spain.
4
Servei de Microscòpia, Universitat Autònoma de Barcelona, Bellaterra 08193 Cerdanyola del Vallès, Barcelona, Spain.
5
CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Spain and Biomedical Research Institute Sant Pau (IIB-Sant Pau) and Josep Carreras Leukemia Research Institute, Hospital de la Santa Creu i Sant Pau, 08025 Barcelona, Spain.

Abstract

Self-assembling proteins are gaining attention as building blocks for application-tailored nanoscale materials. This is mostly due to the biocompatibility, biodegradability, and functional versatility of peptide chains. Such a potential for adaptability is particularly high in the case of recombinant proteins, which are produced in living cells and are suitable for genetic engineering. However, how the cell factory itself and the particular protein folding machinery influence the architecture and function of the final material is still poorly explored. In this study we have used diverse analytical 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 in 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 the features of the producing strain, were found associated with 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 the key parameters and biological performance of the material.

PMID:
28463351
DOI:
10.1039/c6nr09182b

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