Garcia-Fruitos, Elena

Sanchez, Julieta M.

Seras-Franzoso, Joaquin

Unzueta, Ugutz

Frontiers in Bioengineering and Biotechnology

English

IRTA Pubpro

Editorial: High added-valuenanoparticles: Rethinking andrecycling cell protein wasteUgutz Unzueta1,2,3, Julieta M. Sanchez3,4†, Elena Garcia-Fruitós5and Joaquin Seras-Franzoso3,6*1Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain, 2Josep Carreras LeukaemiaResearch Institute (IJC, Campus Sant Pau), Barcelona, Spain, 3CIBER de Bioingeniería, Biomateriales yNanomedicina (CIBER-BBN), Instituto de Salud Carlos III, Madrid, Spain, 4Instituto de InvestigacionesBiológicas y Tecnológicas (IIByT), CONICET- Universidad Nacional de Córdoba, ICTA, FCEFyN, UNC,Córdoba, Argentina, 5Department of Ruminant Production, Institute of Agrifood Research andTechnology (IRTA), Caldes de Montbui, Spain, 6Drug Delivery and Targeting, Vall d’Hebron Institute ofResearch (VHIR), Universitat Autònoma de Barcelona, Barcelona, SpainKEYWORDSnanobiotechnlogy, biomedicine, green biotechnology, Inclusion bodies (IBs),Extracellular vesicles (EVs), virus-based nanomaterialsEditorial on the Research TopicHigh added-value nanoparticles: Rethinking and recycling cell proteinwasteNanotechnology, and specifically the use of nanoparticles (NPs), has been intensivelyexplored during the recent decades in order to solve unmet clinical needs and facedifferent biotechnological challenges. However, their success has been rather modest dueto several limitations associated with the use of current nanomaterials. In this sense, one ofthe aspects in which current NPs have failed is in the development of complexformulations, including biological cues in/onto their surface in a cost-effectivemanner. Moreover, the potential toxicity of the chemicals used for NP synthesis isstill an important safety and environmental concern that prevents the implementation ofmany of such formulations. In this scenario, naturally occurring NPs offer a uniqueopportunity to overcome these biocompatibility, efficacy and cost-effectiveness issues.Production of naturally occurring NPs, synthesized either directly within living cellsor biofabricated through the application of biological catalyzers, have become anappealing source of NPs with value in the biomedical and biotechnological fields.Such technologies provide unique insights, enabling the preparation of complex nano-sized systems, e.g., Inclusion bodies (IBs) or extracellular vesicles (EVs), formed by amilieu of active biomolecules, in relatively simple ways while rendering highlybiocompatible interfaces, optimal for their use in biomedicine. In addition, thediversity in composition and structure of naturally originated NPs empower asignificant number of distinct applications also in the biotechnological field, such astheir use as immobilized biocatalysts or as biosensors for a spectrum of analytes. Thisdiversity is further fueled by the capacity of tailoring natural NPs structure andOPEN ACCESSEDITED AND REVIEWED BYGianni Ciofani,Italian Institute of Technology (IIT), Italy*CORRESPONDENCEJoaquin Seras-Franzoso,joaquin.seras@vhir.org†PRESENT ADDRESSJulieta M. Sanchez,Institut de Biotecnologia i deBiomedicina (IBB), UniversitatAutònoma de Barcelona, Bellaterra,SpainSPECIALTY SECTIONThis article was submitted toNanobiotechnology,a section of the journalFrontiers in Bioengineering andBiotechnologyRECEIVED 12 August 2022ACCEPTED 15 August 2022PUBLISHED 05 September 2022CITATIONUnzueta U, Sanchez JM,Garcia-Fruitós E and Seras-Franzoso J(2022), Editorial: High added-valuenanoparticles: Rethinking and recyclingcell protein waste.Front. Bioeng. Biotechnol. 10:1018014.doi: 10.3389/fbioe.2022.1018014COPYRIGHT© 2022 Unzueta, Sanchez, Garcia-Fruitós and Seras-Franzoso. This is anopen-access article distributed underthe terms of the Creative CommonsAttribution License (CC BY). The use,distribution or reproduction in otherforums is permitted, provided theoriginal author(s) and the copyrightowner(s) are credited and that theoriginal publication in this journal iscited, in accordance with acceptedacademic practice. No use, distributionor reproduction is permittedwhich doesnot comply with these terms.Frontiers in Bioengineering and Biotechnology frontiersin.org01TYPE EditorialPUBLISHED 05 September 2022DOI 10.3389/fbioe.2022.1018014functionality in a bottom-up approach via the geneticmodification of the biological factories. Among the mostcommon naturally occurring NPs we can find protein-onlyNPs, IBs, virus-like particles (VLPs), vaults, EVs,magnetosomes or polymeric particles (PP). Besides, a varietyof metallic NPs can also benefit from the use of bio-catalyzersduring their fabrication. In this regard, the implementation ofgreener synthesis processes is of paramount importance in theactual context of global environmental crisis.Concerning the biomedical context, biocompatibility is oneof the basic traits that any NP must comply with in order to havea chance to progress towards its clinical use. In this sense,Barguilla et al. validated IBs as sub-micron protein particlesdisplaying no cytotoxicity, genotoxicity or oxidative stress overCaco-2 cells, irrespective of the prokaryotic cell factory employedfor their biofabrication. Such reports are very helpful in order toelaborate future product safety profiles and gain insight on theNP/cell interplay. In the same line, but approaching the potentialtoxicity of NPs from a structural perspective, Gil-Garcia andVentura reviewed an intriguing strategy to drive IB formationwhile avoiding the use of potentially toxic amyloid-like domainsto pull down proteins into valuable NPs. Thus, standardrecombinant manipulation would allow to replace the amyloid(highly beta) conformation of natural IBs by a coiled-coil fold,composed of two or more α-helices. This last protein motif iswidely used by nature to create supramolecular assemblies andcould reduce potential undesired side effects derived from theamyloid nature of IBs. Nevertheless, numerous studies reportedno evident toxicity caused by IBs after challenging cell or animalmodels (de Marco et al., 2019) and potential IB derivedcytotoxicity seems to be linked to specific polypeptidesequences and aggregation status (González-Montalbán et al.,2007).Of note, the notorious biocompatibility exhibited by IBs isshared by other types of naturally occurring NPs such as EVs. Inthis regard, EVs are cell membrane bound vesicles secreted byvirtually any cell type that can be exploited as efficient deliverysystems as exemplified by Dong etal. In this instance, the authorstook advantage of EVs properties as natural nanosized drug deliveryplatforms to envisage an original application for EVs derived fromfetal bovine serum (FBS). Serum is a biological fluid extremely richin EVs and therefore a very interesting source for isolating these NPsin enough amounts. Thus, FBS-derived EVs were functionalizedwith Icariin as an alternative way to promote osteoblast proliferationand bone regeneration in vitro, significantly increasing the observedactivity compared to Icariin alone.With respect to the use of natural NPs in green biotechnology,the present issue also includes diverse and interestingcontributions. Shahzadi etal. presented a representative workwhere spherical silver nanoparticles (AgNPs), with differentantioxidant, cytotoxic and antimicrobial activities, wereefficiently generated in a cost-effective and environmentallyfriendly process using plant biotechnology. This is an exampleof how biological systems can be efficiently used as catalyzers forthe biosynthesis of inorganic NPs from externally sourced metalions, avoiding the use of hazardous chemicals generally employedin the production of such materials. Moreover, AgNPs,biofabricated in this fashion, can additionally incorporate plant-derived phytochemicals, conferring novel antioxidant propertiesand expanding thus, the spectrum of biological applications ofgenerated nanomaterials.Another example of green biotechnology is collected here bythe virus-based nanomaterials generated by McNulty et al. asreagents for therapeutic protein purification. In this work, virus-based immunosorbent nanoparticles, generated using plant-based manufacturing and virus-functionalized magneticparticles were shown as a potential alternative to thetraditional chemical methods used in the biopharmaceuticalindustry. Of note, such assemblies showed an extraordinarybinding affinity capacity for therapeutic proteins.Finally, a novel usage for bacterial IBs as potential biosensorshas been described by Hrabarova etal. This work is yet anotherexample of the enormous potential exhibited by cell proteinwaste NPs to be re-formulated in order to achieve new objectives.In this regard, the authors successfully engineered a highlysoluble green fluorescent protein to produce bioactive IBswith an increased sensitivity to metals and di-/tri-inorganicphosphates. Their approach was based on the addition ofsmall aggregation-prone peptide tags that also show modifiedsensitivity for poly-phosphates and metals ions. Thus, the sametype of biosensors could be used to detect the presence of metalions such as Cu2+, Zn2+ or Hg2+ in environmental samples or tomonitor pyrophosphates levels in plasma, which possess value asa biomarker for various diseases.All in all, the present research topic reflects the growinginterest of natural NPs for different biomedical andbiotechnological purposes, where novel applications aresteadily appearing and main limitations, e.g., toxicity studies,are being tackled. However, some issues such as: standardizationof natural NPs characterization, cumbersome scaling upprocesses or further understanding of body responses to longterm exposure should still be addressed in order to fully fulfill thepromise of such NPs.Author contributionsJS-F and UU prepared the first draft. All the authorscontributed to and revised the final manuscript.Conflict of interestJS-F, EG-F, UU, and JS all hold pending or confirmedpatents. UU patents are licensed to the start-up companyNanoligent, SL.Frontiers in Bioengineering and Biotechnology frontiersin.org02Unzueta et al. 10.3389/fbioe.2022.1018014Publisher’s noteAll claims expressed in this article are solely those of theauthors and do not necessarily represent those of their affiliatedorganizations, or those of the publisher, the editors and thereviewers. Any product that may be evaluated in this article, orclaim that may be made by its manufacturer, is not guaranteed orendorsed by the publisher.Referencesde Marco, A., Ferrer-Miralles, N., Garcia-Fruitós, E., Mitraki, A., Peternel, S.,Rinas, U., et al. (2019). Bacterial inclusion bodies are industrially exploitableamyloids. FEMS Microbiol. Rev. 43, 53–72. [Internet]Available at: doi:10.1093/femsre/fuy038González-Montalbán, N., Villaverde, A., and Aris, A. (2007). Amyloid-linkedcellular toxicity triggered by bacterial inclusion bodies. Biochem. Biophys. Res.Commun. 355, 637–642. [Internet]Available from:. doi:10.1016/j.bbrc.2007.01.192Frontiers in Bioengineering and Biotechnology frontiersin.org03Unzueta et al. 10.3389/fbioe.2022.1018014

Editorial: High added-value nanoparticles: Rethinking and recycling cell protein waste

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Editorial: High added-value nanoparticles: Rethinking and recycling cell protein waste

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