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Image-guided nanodelivery of Pt(IV) prodrugs to GRP-receptor positive tumors

2023-01Journal article Open access
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dc.contributor.authorSilva, Francisco
dc.contributor.authorMendes, Carolina
dc.contributor.authorD'Onofrio, Alice
dc.contributor.authorCampello, Maria Paula Cabral
dc.contributor.authorMarques, Fernanda
dc.contributor.authorPinheiro, Teresa
dc.contributor.authorGonçalves, Kyle
dc.contributor.authorFigueiredo, Sérgio
dc.contributor.authorGano, Lurdes
dc.contributor.authorRavera, Mauro
dc.contributor.authorGabano, Elisabetta
dc.contributor.authorPaulo, António
dc.date.accessioned2022-12-15T10:57:04Z
dc.date.available2022-12-15T10:57:04Z
dc.date.issued2023-01
dc.description.abstractOver the last decades, gold nanoparticles (AuNPs) have proven to be remarkable tools for drug delivery and theranostic applications in cancer treatment. On the other hand, Pt(IV) prodrugs have been employed as an interesting alternative to the more common Pt(II) complexes, such as cisplatin, for cancer chemotherapy. Searching to design an image-guided nanocarrier to deliver selectively Pt(IV) prodrugs to tumors expressing the gastrin-releasing peptide receptor (GRPR), we have synthesized small core AuNPs carrying a thiolated DOTA derivative, a GRPR-targeting bombesin analog (BBN[7-14]) and a Pt(IV) prodrug attached to the AuNPs without (AuNP-BBN-Pt1) or with a PEGylated linker (AuNP-BBN-Pt2 and AuNP-BBN-Pt3). In the GRPR+ prostate cancer PC3 cell line, the cytotoxic activity of the designed AuNP-BBN-Pt nanoparticles is strongly influenced by the presence of the PEGylated linker. Thus, AuNP-BBN-Pt1 displayed the lowest IC50 value (9.3 ± 2.3 µM of Pt), which is comparable to that exhibited by cisplatin in the same cell line. In contrast, AuNP-BBN-Pt1 showed an IC50 value of 97 ± 18 µM of Pt in the non-tumoral RWPE-1 prostate cells with a much higher selective index (SI) towards PC3 cells (SI = 10) when compared with cisplatin (SI = 1.3). The AuNPs were also successfully labeled with 67Ga and the resulting 67Ga-AuNP-BBN-Pt were used to assess their cellular uptake in PC3 cells, with AuNP-BBN-Pt1 also displaying the highest cellular internalization. Finally, intratumoral administration of 67Ga-AuNP-BBN-Pt1 in PC3 tumor-bearing mice showed prolonged retention of the nanoparticle compared to that of cisplatin, with optimal in vivo stability and 20% of the injected platinum remaining in the tumor after 72 h post-injection. Furthermore, microSPECT imaging studies confirmed the uptake and considerable retention of the 67Ga-labeled AuNPs in the tumors. Overall, these results show the potential of these targeted AuNPs loaded with Pt(IV) prodrugs for prostate cancer theranostics.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationSilva F, Mendes C, D'Onofrio A, Campello MP, Figueiredo S, Paulo A, et al. Image-guided nanodelivery of Pt(IV) prodrugs to GRP-receptor positive tumors. Nanotheranostics. 2023;7(1):22-40.pt_PT
dc.identifier.doi10.7150/ntno.78807pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.21/15152
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherNTNOpt_PT
dc.relation.publisherversionhttps://www.ntno.org/v07p0022.htmpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectGold nanoparticlespt_PT
dc.subjectBombesin peptidespt_PT
dc.subjectPt(IV) prodrugspt_PT
dc.subject67Gapt_PT
dc.subjectProstate cancerpt_PT
dc.titleImage-guided nanodelivery of Pt(IV) prodrugs to GRP-receptor positive tumorspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage40pt_PT
oaire.citation.issue1pt_PT
oaire.citation.startPage22pt_PT
oaire.citation.titleNanotheranosticspt_PT
oaire.citation.volume7pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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