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| Home > Articles > Published articles > Intrinsic functional and architectonic heterogeneity of tumor-targeted protein nanoparticles |
(Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí") (ALBA Laboratori de Llum de Sincrotró) (Universitat Autònoma de Barcelona. Servei de Microscòpia) (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí") (Institut d'Investigació Biomèdica Sant Pau) (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí") (Institut d'Investigació Biomèdica Sant Pau) (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia) (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí") (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)| Date: | 2017 |
| 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. |
| Grants: | Ministerio de Economía y Competitividad BIO2013-41019-P Instituto de Salud Carlos III PI15/00378 Instituto de Salud Carlos III PI15/00272 Agència de Gestió d'Ajuts Universitaris i de Recerca 2016/FI_B 00034 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014/SGR-132 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014/PROD 00055 |
| Note: | Altres ajuts: CIBER de Bioingeniería, Biomateriales y Nanomedicina (project NANOPROTHER) (to AV), Marató de TV3 foundation (TV32013-132031) (TV32013-133930). Protein production has been partially performed by the ICTS "NANBIOSIS", more specifically by the Protein Production Platform of CIBER in Bioengineering, Biomaterials & Nanomedicine (CIBER-BBN)/IBB, at the UAB SepBioES scientific-technical service (http://www.nanbiosis.es/unit/u1-protein-production-platform-ppp/) and DLS measurements have been done at the Biomaterial Processing and Nanostructuring Unit of NANBIOSIS. We are also indebted to Fran Cortés from the Cell Culture and Cytometry Units of the Servei de CultiusCel·lulars, Producciód'AnticossosiCitometria (SCAC), and to the Servei de Microscòpia, both at the UAB. Strain KPM335 was kindly provided by Research Corporation Technologies, Tucson, AZ. AV received an ICREA ACADEMIA award. |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Subject: | Analytical approach ; Biological performance ; Field emission scanning electron microscopy ; Fluorescence emission ; Nano-scale materials ; Optimal properties ; Specificity profile ; Targeted proteins ; Cell Line, Tumor ; Drug Carriers ; Fluorescence ; Green Fluorescent Proteins ; HeLa Cells ; Humans ; Microscopy, Electron, Scanning ; Nanoparticles ; Neoplasms ; Recombinant Proteins ; Scattering, Small Angle ; X-Ray Diffraction |
| Published in: | Nanoscale, Vol. 9, issue 19 (May 2017) , p. 6427-6435, ISSN 2040-3372 |
