105 research outputs found
Microwave Synthesis of Visible-Light-Activated g-C3N4/TiO2 Photocatalysts
Funding Information: This work was financed by national funds from FCT-Fundação para a Ciência e a Tecnologia, I.P., within the scope of projects UI/BD/151292/2021 (Ph.D. research scholarship), LA/P/0037/2020, UIDP/50025/2020 and UIDB/50025/2020 of the Associate Laboratory Institute of Nanostructures, Nanomodelling, and Nanofabrication-i3N, but also the 2021.03825.CEECIND. Acknowledgments are also given to the EC project SYNERGY H2020-WIDESPREAD-2020-5, CSA, proposal nº 952169, EMERGE-2020-INFRAIA-2020-1, proposal nº 101008701, and to the European Community’s H2020 program under grant agreement No. 787410 (ERC-2018-AdG DIGISMART). Publisher Copyright: © 2023 by the authors.The preparation of visible-light-driven photocatalysts has become highly appealing for environmental remediation through simple, fast and green chemical methods. The current study reports the synthesis and characterization of graphitic carbon nitride/titanium dioxide (g-C3N4/TiO2) heterostructures through a fast (1 h) and simple microwave-assisted approach. Different g-C3N4 amounts mixed with TiO2 (15, 30 and 45 wt. %) were investigated for the photocatalytic degradation of a recalcitrant azo dye (methyl orange (MO)) under solar simulating light. X-ray diffraction (XRD) revealed the anatase TiO2 phase for the pure material and all heterostructures produced. Scanning electron microscopy (SEM) showed that by increasing the amount of g-C3N4 in the synthesis, large TiO2 aggregates composed of irregularly shaped particles were disintegrated and resulted in smaller ones, composing a film that covered the g-C3N4 nanosheets. Scanning transmission electron microscopy (STEM) analyses confirmed the existence of an effective interface between a g-C3N4 nanosheet and a TiO2 nanocrystal. X-ray photoelectron spectroscopy (XPS) evidenced no chemical alterations to both g-C3N4 and TiO2 at the heterostructure. The visible-light absorption shift was indicated by the red shift in the absorption onset through the ultraviolet-visible (UV-VIS) absorption spectra. The 30 wt. % of g-C3N4/TiO2 heterostructure showed the best photocatalytic performance, with a MO dye degradation of 85% in 4 h, corresponding to an enhanced efficiency of almost 2 and 10 times greater than that of pure TiO2 and g-C3N4 nanosheets, respectively. Superoxide radical species were found to be the most active radical species in the MO photodegradation process. The creation of a type-II heterostructure is highly suggested due to the negligible participation of hydroxyl radical species in the photodegradation process. The superior photocatalytic activity was attributed to the synergy of g-C3N4 and TiO2 materials.publishersversionpublishe
A Novel Function
Funding Information: This work was supported by Fundação para a Ciência e Tecnologia, Ministério da Ciência, Tecnologia e Ensino Superior (FCT-MCTES), through the grant number PTDC/QUI/64248/2006 (to A.S.P.), the Radiation Biology and Biophysics Doctoral Training Programme—RaBBiT (PD/00193/2012), Applied Molecular Biosciences Unit—UCIBIO (UIDP/04378/2020, i4HB—Institute for Health and Bioeconomy (LA/P/0140/2020) and CEFITEC (UIDB/00068/2020). A.V.A. (PD/BD/135477/2017 and COVID/BD/152498/2022) is supported by the RaBBiT programme. This work benefited from STSM funding by COST Action (CA15126 MOBIEU) and by the project CALIPSOplus under the Grant Agreement 730872 from the EU Framework Programme for Research and Innovation HORIZON 2020. Publisher Copyright: © 2022 by the authors.Encapsulins are protein nanocages capable of harboring smaller proteins (cargo proteins) within their cavity. The function of the encapsulin systems is related to the encapsulated cargo proteins. The Myxococcus xanthus encapsulin (EncA) naturally encapsulates ferritin-like proteins EncB and EncC as cargo, resulting in a large iron storage nanocompartment, able to accommodate up to 30,000 iron atoms per shell. In the present manuscript we describe the binding and protection of circular double stranded DNA (pUC19) by EncA using electrophoretic mobility shift assays (EMSA), atomic force microscopy (AFM), and DNase protection assays. EncA binds pUC19 with an apparent dissociation constant of 0.3 ± 0.1 µM and a Hill coefficient of 1.4 ± 0.1, while EncC alone showed no interaction with DNA. Accordingly, the EncAC complex displayed a similar DNA binding capacity as the EncA protein. The data suggest that initially, EncA converts the plasmid DNA from a supercoiled to a more relaxed form with a beads-on-a-string morphology. At higher concentrations, EncA self-aggregates, condensing the DNA. This process physically protects DNA from enzymatic digestion by DNase I. The secondary structure and thermal stability of EncA and the EncA−pUC19 complex were evaluated using synchrotron radiation circular dichroism (SRCD) spectroscopy. The overall secondary structure of EncA is maintained upon interaction with pUC19 while the melting temperature of the protein (Tm) slightly increased from 76 ± 1 °C to 79 ± 1 °C. Our work reports, for the first time, the in vitro capacity of an encapsulin shell to interact and protect plasmid DNA similarly to other protein nanocages that may be relevant in vivo.publishersversionpublishe
Floating TiO2-Cork Nano-Photocatalysts for Water Purification Using Sunlight
Funding Information: This work was financed by national funds from FCT—Fundação para a Ciência e a Tecnologia, I.P., in the scope of the projects LA/P/0037/2020, UIDP/50025/2020, and UIDB/50025/2020 of the Associate Laboratory Institute of Nanostructures, Nanomodelling, and Nanofabrication—i3N, but also the UI/BD/151292/2021 (Ph.D. research scholarship). The work was also partially funded by the Nanomark collaborative project between INCM (Imprensa Nacional—Casa da Moeda) and CENIMAT/i3N. Acknowledgments also go to the EC project SYNERGY H2020-WIDESPREAD-2020-5, CSA, proposal nº 952169, EMERGE-2020-INFRAIA-2020-1, proposal nº 101008701, and to the European Community’s H2020 program under grant agreement No. 787410 (ERC-2018-AdG DIGISMART). Publisher Copyright: © 2022 by the authors.In the present study, titanium dioxide (TiO2) nano-photocatalysts were synthesized through microwave irradiation. In a typical microwave synthesis, TiO2 nanomaterials were simultaneously produced in powder form and also directly covering cork substrates. The TiO2 nanopowder was analyzed by X-ray diffraction (XRD), Raman spectroscopy and transmission electron microscopy (TEM), revealing that the solvothermal microwave synthesis resulted only in the TiO2 anatase phase. From Fourier-transform infrared spectroscopy (FTIR), cork’s organic species, along with bands of TiO2, were detected. UV–VIS absorption spectrum revealed an absorption extension to the visible region, since a brown powdered TiO2 product was obtained. Very fine nanoparticles were observed displaying a nearly spherical shape that agglomerates in larger particles. These larger particles fully covered the surface of the honeycomb cork cells, originating TiO2 functionalized cork platforms. The TiO2 functionalized substrates were further tested as floating photocatalysts and their photocatalytic activity was assessed from rhodamine B degradation under solar simulating light and natural sunlight. Reusability tests were also performed under natural sunlight. The strategy applied in this research work allowed the production of green and low-cost cork platforms based on TiO2 photoactive materials with the ability to purify polluted water under natural sunlight.publishersversionpublishe
Transcriptomic leaf profiling reveals differential responses of the two most traded coffee species to elevated [co2]
PTDC/ASP-AGR/31257/2017
UIDB/00239/2020
UIDP/04035/2020
UID/AGR/04129/2020
UIDB/04551/2020
CRA-RED-00053-16As atmospheric [CO2] continues to rise to unprecedented levels, understanding its impact on plants is imperative to improve crop performance and sustainability under future climate conditions. In this context, transcriptional changes promoted by elevated CO2 (eCO2) were studied in genotypes from the two major traded coffee species: the allopolyploid Coffea arabica (Icatu) and its diploid parent, C. canephora (CL153). While Icatu expressed more genes than CL153, a higher number of differentially expressed genes were found in CL153 as a response to eCO2. Although many genes were found to be commonly expressed by the two genotypes under eCO2, unique genes and pathways differed between them, with CL153 showing more enriched GO terms and metabolic pathways than Icatu. Divergent functional categories and significantly enriched pathways were found in these genotypes, which altogether supports contrasting responses to eCO2. A considerable number of genes linked to coffee physiological and biochemical responses were found to be affected by eCO2 with the significant upregulation of photosynthetic, antioxidant, and lipidic genes. This supports the absence of photosynthesis down-regulation and, therefore, the maintenance of increased photosynthetic potential promoted by eCO2 in these coffee genotypes.publishersversionpublishe
BFF: A tool for eliciting tie strength and user communities in social networking services
The final publication is available at Springer via http://dx.doi.org/ 10.1007/s10796-013-9453-6The use of social networking services (SNSs) such as Facebook has explosively grown in the last few years. Users see these SNSs as useful tools to find friends and interact with them. Moreover, SNSs allow their users to share photos, videos, and express their thoughts and feelings. However, users are usually concerned about their privacy when using SNSs. This is because the public image of a subject can be affected by photos or comments posted on a social network. In this way, recent studies demonstrate that users are demanding better mechanisms to protect their privacy. An appropriate approximation to solve this could be a privacy assistant software agent that automatically suggests a privacy policy for any item to be shared on a SNS. The first step for developing such an agent is to be able to elicit meaningful information that can lead to accurate privacy policy predictions. In particular, the information needed is user communities and the strength of users' relationships, which, as suggested by recent empirical evidence, are the most important factors that drive disclosure in SNSs. Given the number of friends that users can have and the number of communities they may be involved on, it is infeasible that users are able to provide this information without the whole eliciting process becoming confusing and time consuming. In this work, we present a tool called Best Friend Forever (BFF) that automatically classifies the friends of a user in communities and assigns a value to the strength of the relationship ties to each one. We also present an experimental evaluation involving 38 subjects that showed that BFF can significantly alleviate the burden of eliciting communities and relationship strength.This work has been partially supported by CONSOLIDER-INGENIO 2010 under grant CSD2007-00022, and TIN 2008-04446 and PROMETEO II/2013/019 projects. This article has been developed as a result of a mobility stay funded by the Erasmus Mundus Programme of the European Comission under the Transatlantic Partnership for Excellence in Engineering - TEE Project.López Fogués, R.; Such Aparicio, JM.; Espinosa Minguet, AR.; García-Fornes, A. (2014). BFF: A tool for eliciting tie strength and user communities in social networking services. Information Systems Frontiers. 16:225-237. https://doi.org/10.1007/s10796-013-9453-6S22523716Blondel, V.D., Guillaume, J.L., Lambiotte, R., Lefebvre, E. (2008). Fast unfolding of communities in large networks. Journal of Statistical Mechanics: Theory and Experiment, 2008(10), P10008.Boyd, D., & Hargittai, E. (2010). Facebook privacy settings: who cares? First Monday, 15(8).Burt, R. (1995). Structural holes: the social structure of competition. Harvard University Pr.Culotta, A., Bekkerman, R., McCallum, A. (2004). Extracting social networks and contact information from email and the web.Ellison, N., Steinfield, C., Lampe, C. (2007). The benefits of facebook friends: social capital and college students use of online social network sites. Journal of Computer-Mediated Communication, 12(4), 1143–1168.Fang, L., & LeFevre, K. (2010). Privacy wizards for social networking sites. In Proceedings of the 19th international conference on World wide web (pp. 351–360). ACM.Fortunato, S. (2010). Community detection in graphs. Physics Reports, 486(3-5), 75–174.Gilbert, E., & Karahalios, K. (2009). Predicting tie strength with social media. In Proceedings of the 27th international conference on human factors in computing systems (pp. 211–220). ACM.Girvan, M., & Newman, M. (2002). Community structure in social and biological networks. Proceedings of the National Academy of Science, 99(12), 7821.Granovetter, M. (1973). The strength of weak ties. American Journal of Sociology, 1360–1380.Gross, R., & Acquisti, A. (2005). Information revelation and privacy in online social networks. In Proceedings of the 2005 ACM workshop on privacy in the electronic society (pp. 71–80). ACM.Johnson, M., Egelman, S., Bellovin, S. (2012). Facebook and privacy: it’s complicated. In Proceedings of the eighth symposium on usable privacy and security (p. 9). ACM .Kahanda, I., & Neville, J. (2009). Using transactional information to predict link strength in online social networks. In Proceedings of the third international conference on weblogs and social media (ICWSM).Lancichinetti, A., & Fortunato, S. (2009). Community detection algorithms: a comparative analysis. Physical Review E, 80, 056–117.Lancichinetti, A., Fortunato, S., Kertsz, J. (2009). Detecting the overlapping and hierarchical community structure in complex networks. New Journal of Physics, 11(3), 033–015.Lin, N., Ensel, W., Vaughn, J. (1981). Social resources and strength of ties: Structural factors in occupational status attainment. American Sociological Review, 393–405.Lipford, H., Besmer, A., Watson, J. (2008). Understanding privacy settings in facebook with an audience view. In Proceedings of the 1st conference on usability, psychology, and security (pp. 1–8). Berkeley: USENIX Association.Liu, G., Wang, Y., Orgun, M. (2010). Optimal social trust path selection in complex social networks. In Proceedings of the 24th AAAI conference on artificial intelligence (pp. 139–1398). AAAI.Matsuo, Y., Mori, J., Hamasaki, M., Nishimura, T., Takeda, H., Hasida, K., Ishizuka, M. (2007). Polyphonet: an advanced social network extraction system from the web. Web Semantics: Science, Services and Agents on the World Wide Web, 5(4), 262–278. World Wide Web Conference 2006 Semantic Web Track.Murukannaiah, P., & Singh, M. (2011). Platys social: relating shared places and private social circles. Internet Computing IEEE, 99, 1–1.Quercia, D., Lambiotte, R., Kosinski, M., Stillwell, D., Crowcroft, J. (2012). The personality of popular facebook users. In Proceedings of the ACM 2012 conference on computer supported cooperative work (CSCW’12).Rosvall, M., & Bergstrom, C. (2008). Maps of random walks on complex networks reveal community structure. Proceedings of the National Academy of Sciences, 105(4), 1118–1123.Sharma, G., Qiang, Y., Wenjun, S., Qi, L. (2013). Communication in virtual world: Second life and business opportunities. Information Systems Frontiers, 15(4), 677–694.Shen, K., Song, L., Yang, X., Zhang, W. (2010). A hierarchical diffusion algorithm for community detection in social networks. In 2010 international conference on cyber-enabled distributed computing and knowledge discovery (CyberC) (pp. 276–283). IEEE.Sierra, C., & Debenham, J. (2007). The LOGIC negotiation model. In AAMAS ’07: proceedings of the 6th international joint conference on autonomous agents and multiagent systems (pp. 1–8). ACM.Staddon, J., Huffaker, D., Brown, L., Sedley, A. (2012). Are privacy concerns a turn-off?: engagement and privacy in social networks. In Proceedings of the eighth symposium on usable privacy and security (p. 10). ACM.Strater, K., & Lipford, H.R. (2008). Strategies and struggles with privacy in an online social networking community. In Proceedings of the 22nd British HCI group annual conference on people and computers: culture, creativity, interaction, BCS-HCI ’08 (Vol. 1, pp. 111–119). Swinton: British Computer Society.Wellman, B., & Wortley, S. (1990). Different strokes from different folks: Community ties and social support. American Journal of Sociology, 558–588.Wiese, J., Kelley, P., Cranor, L., Dabbish, L., Hong, J., Zimmerman, J. (2011). Are you close with me? are you nearby? investigating social groups, closeness, and willingness to share. In Proceedings of the 13th international conference on Ubiquitous computing (pp. 197–206). ACM.Xiang, R., Neville, J., Rogati, M. (2010). Modeling relationship strength in online social networks. In Proceedings of the 19th international conference on World wide web (pp. 981–990). ACM
Protective Response Mechanisms to Heat Stress in Interaction with High [CO2] Conditions in Coffea spp.
This work was supported by national funds from Fundacao para a Ciencia e a Tecnologia through the projects PTDC/AGRPRO/3386/2012, the research units UID/AGR/04129/2013 (LEAF) and UID/GEO/04035/2013 (GeoBioTcc), as well through the grant SFRH/BPD/47563/2008 (AT) co-financed through the POPH program subsidized by the European Social Fund. Brazilian funding from CAPES (grams PDSE: 000427/2014-04, W.P. Rodrigues; 0343/2014-05, MM; 12226/12-2, LM), CNPq and Fapemig (fellowships to FDM, FP, and EC) are also greatly acknowledged.Modeling studies have predicted that coffee crop will be endangered by future global warming, but recent reports highlighted that high [CO2] can mitigate heat impacts on coffee. This work aimed at identifying heat protective mechanisms promoted by CO2 in Coffea arabica (cv. Icatu and IPR108) and Coffea canephora cv. Conilon CL153. Plants were grown at 25/20 degrees C (day/night), under 380 or 700 mu L CO2 L-1, and then gradually submitted to 31/25, 37/30, and 42/34 degrees C. Relevant heat tolerance up to 37/30 degrees C for both [CO2] and all coffee genotypes was observed, likely supported by the maintenance or increase of the pools of several protective molecules (neoxanthin, lutein, carotenes, ohtocopherol, HSP70, raffinose), activities of antioxidant enzymes, such as superoxide dismutase (SOD), ascorbate peroxidase (APX), glutathione reductase (GR), catalase (CAT), and the upregulated expression of some genes (ELIP, Chaperonin 20). However, at 42/34 degrees C a tolerance threshold was reached, mostly in the 380 -plants and Icatu. Adjustments in raffinose, lutein, beta-carotene, alpha-tocopherol and HSP70 pools, and the upregulated expression of genes related to protective (FLIPS, HSP70, Chape 20, and 60) and antioxidant (CAT, CuSOD2, APX Cyt, APX ChI) proteins were largely driven by temperature. However, enhanced [CO2] maintained higher activities of GR (Icatu) and CAT (Icatu and IPR108), kept (or even increased) the Cu,Zn-SOD, APX, and CAT activities, and promoted a greater upregulation of those enzyme genes, as well as those related to HSP70, ELIPs, Chaperonins in CL153, and Icatu. These changes likely favored the maintenance of reactive oxygen species (ROS) at controlled levels and contributed to mitigate of photosystem II photoinhibition at the highest temperature. Overall, our results highlighted the important role of enhanced [CO2] on the coffee crop acclimation and sustainability under predicted future global warming scenarios.publishersversionpublishe
Lipid profile adjustments may contribute to warming acclimation and to heat impact mitigation by elevated [CO2] in Coffea spp
This work was supported by European Union, Program Horizon 2020, call H2020-SFS-2016-2, action RIA, and Portuguese national funds from Fundacao para a Ciencia e a Tecnologia (project PTDC/ASP-AGR/31257/2017;
Funding from CNPq (fellowships to E. Campostrini, F.L. Partelli, and F.M. DaMatta) is also acknowledged.An unexpected heat resilience, and the mitigation of heat impacts by elevated [CO2] were recently reported in Coffea spp. Plants must maintain membrane fluidity and integrity to cope with temperature changes, which requires an adequate lipid dynamics. This work provides the lipid profile (galactolipids, GL; phospholipids, PL; sulfolipids, SL) of chloroplast membranes, and the expression of a set of genes related to lipid metabolism in Coffea arabica L. (cv. Icatu and IPR108) and C. canephora cv. Conilon CL153, under elevated [CO2] (380 or 700 μL L−1), heat (25/20, 31/25, 37/30 and 42/34 °C, day/night) and their interaction. Major membrane lipids alterations, different among genotypes, included: A) responsiveness of total fatty acids (TFAs) synthesis to [CO2] (except IPR108) and heat (except CL153); stronger remodeling (unsaturation degree) in the 700-plants from 37/30 °C to 42/34 °C, coordinated at transcriptional level with the down-regulation of fatty acid desaturase FAD3 gene (C. arabica) and up-regulation of lipoxygenase genes LOX5A (CL153 and Icatu) and LOX5B (Icatu) at the highest temperature; B) quantitative and qualitative modifications in GL (monogalactosyldiacylglycerol, MGDG; digalactosyldiacylglycerol, DGDG), PL (phosphatidylcholine, PC; phosphatidylglycerol, PG), and SL (sulfoquinovosyldiacylglycerol, SQDG) classes, prompted by heat, elevated [CO2], and, especially, the interaction, in CL153 and Icatu. Overall membrane enrichment with MGDG and DGDG as a result of heat and [CO2] interaction in these genotypes, but at the highest temperature only in Icatu the high [CO2] maintained greater contents and unsaturation values of these GLs than in the 380-plants. C) Among PL classes, PG seems to play an active role in heat acclimation of C. arabica genotypes, increasing in 700-plants at 42/34 °C. Globally, Icatu often showed changes closer to those of heat tolerant cv. CL153 than to cv. IPR108. Overall, lipid profile adjustments in chloroplast membranes, from TFAs bulk until FA unsaturation within each class, are expected to contribute to long-term acclimation to climate changes in coffee plant.publishersversionpublishe
Estratégias fotónicas para fotovoltaico : novos avanços para além da ótica
CIES2020 - XVII Congresso Ibérico e XIII Congresso Ibero-americano de Energia SolarRESUMO: Estruturas fotónicas com tamanhos comparáveis aos comprimentos de onda da luz solar são as soluções preferenciais para melhorar a eficiência de dispositivos fotovoltaicos através de aprisionamento de luz. As micro-estruturas fotónicas aqui desenvolvidas operam no regime de ótica de ondas, pelo que foram construídos modelos eletromagnéticos que permitiram encontrar os parâmetros ótimos para aplicação no contacto frontal de diferentes tipos de tecnologias, nomeadamente em células de filme fino baseadas em silício ou perovskite. Desta forma, foram obtidas diferentes arquiteturas fotónicas de células, demonstrando melhoras de até 50% na eficiência relativamente a células de referência planas. Os resultados mostram que as vantagens da aplicação de estruturas fotónicas não estão só limitadas a ganhos óticos de melhora da absorção, mas também possibilitam outros benefícios importantes tais como: ganhos elétricos devido à melhora dos contactos transparentes, e melhor desempenho em condições ambientais devido a um encapsulamento avançado dos dispositivos que confere até propriedades de auto-limpeza dos mesmos.ABSTRACT: Photonic structures with dimensions comparable to the sunlight wavelengths are now regarded as the preferential solutions to enhance the efficiency of photovoltaic devices via light trapping. The photonic microstructures operate in the regime of wave-optics, so electromagnetic models were constructed that were capable of determining the optimal parameters for application in the front contact of different photovoltaic technologies, namely in thin film solar cells based in silicon or perovskite materials. In this way, distinct photonic cell architectures were obtained, showing efficiency improvements up to 50% with respect to planar reference solar cells. The results demonstrate that the advantages in the application of the photonic structures are not just limited to optical gains related with light absorption enhancement, but also enable other important benefits such as: electrical gains due to the improvement of the front contact conductance, and better environmental/outdoor performance due to an advanced micro-structured encapsulation that even allows self-cleaning properties.info:eu-repo/semantics/publishedVersio
A comprehensive assessment of the transcriptome of cork oak (Quercus suber) through EST sequencing
Background: Cork oak (Quercus suber) is one of the rare trees with the ability to produce cork, a material widely used to make wine bottle stoppers, flooring and insulation materials, among many other uses. The molecular mechanisms of cork formation are still poorly understood, in great part due to the difficulty in studying a species with a long life-cycle and for which there is scarce molecular/genomic information. Cork oak forests are of great ecological importance and represent a major economic and social resource in Southern Europe and Northern Africa. However, global warming is threatening the cork oak forests by imposing thermal, hydric and many types of novel biotic stresses. Despite the economic and social value of the Q. suber species, few genomic resources have been developed, useful for biotechnological applications and improved forest management.
Results: We generated in excess of 7 million sequence reads, by pyrosequencing 21 normalized cDNA libraries derived from multiple Q. suber tissues and organs, developmental stages and physiological conditions. We deployed a stringent sequence processing and assembly pipeline that resulted in the identification of ~159,000 unigenes. These were annotated according to their similarity to known plant genes, to known Interpro domains, GO classes and E.C. numbers. The phylogenetic extent of this ESTs set was investigated, and we found that cork oak revealed a significant new gene space that is not covered by other model species or EST sequencing projects. The raw data, as well as the full annotated assembly, are now available to the community in a dedicated web portal at http://www.corkoakdb.org.
Conclusions: This genomic resource represents the first trancriptome study in a cork producing species. It can be explored to develop new tools and approaches to understand stress responses and developmental processes in forest trees, as well as the molecular cascades underlying cork differentiation and disease response.Peer Reviewe
Targeted molecular-genetic imaging and ligand-directed therapy in aggressive variant prostate cancer
Aggressive variant prostate cancers (AVPC) are a clinically defined group of tumors of heterogeneous morphologies, characterized by poor patient survival and for which limited diagnostic and treatment options are currently available. We show that the cell surface 78-kDa glucose-regulated protein (GRP78), a receptor that binds to phage-display-selected ligands, such as the SNTRVAP motif, is a candidate target in AVPC. We report the presence and accessibility of this receptor in clinical specimens from index patients. We also demonstrate that human AVPC cells displaying GRP78 on their surface could be effectively targeted both in vitro and in vivo by SNTRVAP, which also enabled specific delivery of siRNA species to tumor xenografts in mice. Finally, we evaluated ligand-directed strategies based on SNTRVAP-displaying adeno-associated virus/phage (AAVP) particles in mice bearing MDA-PCa-118b, a patient-derived xenograft (PDX) of castration-resistant prostate cancer bone metastasis that we exploited as a model of AVPC. For theranostic (a merging of the terms therapeutic and diagnostic) studies, GRP78-targeting AAVP particles served to deliver the human Herpes simplex virus thymidine kinase type-1 (HSVtk) gene, which has a dual function as a molecular-genetic sensor/reporter and a cell suicide-inducing transgene. We observed specific and simultaneous PET imaging and treatment of tumors in this preclinical model of AVPC. Our findings demonstrate the feasibility of GPR78-targeting, ligand-directed theranostics for translational applications in AVPC
- …