Artigo De: scopus, orcid, cienciavitae
Image-Guided Nanodelivery of Pt(IV) Prodrugs to GRP-Receptor Positive Tumors
Nanotheranostics
2023 — Ivyspring
—Informações chave
Autores:
Publicado em
01/01/2023
Resumo
Over 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 a PC3 tumor-bearing mice showed a 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.
Detalhes da publicação
Autores da comunidade :
Fernanda Marujo Marques
ist25359
António Manuel Rocha Paulo
ist126677
Versão da publicação
AO - Versão original do autor
Editora
Ivyspring
Ligação para a versão da editora
https://www.ntno.org/v7i2
Título do contentor da publicação
Nanotheranostics
Primeira página ou número de artigo
22
Última página
40
Volume
7
Fascículo
1
ISSN
2206-7418
Domínio Científico (FOS)
health-sciences - Ciências de Saúde
Palavras-chave
- gold nanoparticles
- bombesin peptides
- Pt(IV) prodrugs
- 67Ga
- prostate cancer
Idioma da publicação (código ISO)
eng - Inglês
Identificador alternativo (URI)
http://dx.doi.org/10.7150/ntno.78807
Acesso à publicação:
Acesso apenas a metadados
Licença Creative Commons
CC-BY - CC-BY