Nanotheranostics 2023; 7(1):22-40. doi:10.7150/ntno.78807 This issue Cite

Research Paper

Image-Guided Nanodelivery of Pt(IV) Prodrugs to GRP-Receptor Positive Tumors

Francisco Silva1✉, Carolina Mendes1, Alice D'Onofrio1, Maria Paula Cabral Campello1,2, Fernanda Marques1,2, Teresa Pinheiro2,3, Kyle Gonçalves1, Sérgio Figueiredo4,5, Lurdes Gano1,2, Mauro Ravera6, Elisabetta Gabano7, António Paulo1,2✉

1. Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Campus Tecnológico e Nuclear, Estrada Nacional 10, Km 139.7, 2695-066 Bobadela LRS, Portugal.
2. Departamento de Engenharia e Ciências Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Portugal.
3. iBB - Instituto de Bioengenharia e Biociências, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais 1, 1049-001 Lisboa, Portugal.
4. Institute for Systems and Robotics (ISR), LARSyS, Instituto Superior Técnico, Department of Bioengineering, Universidade de Lisboa, Portugal
5. H&TRC - Health &Technology Research Center, ESTeSL/IPL - Escola Superior de Tecnologia da Saúde de Lisboa/Instituto Politécnico de Lisboa, Portugal.
6. Dipartimento di Scienze e Innovazione Tecnologica, Università del Piemonte Orientale, Viale Teresa Michel 11, 15121 Alessandria, Italy.
7. Dipartimento per lo Sviluppo Sostenibile e la Transizione Ecologica, Università del Piemonte Orientale, Piazza Sant'Eusebio 5, 13100 Vercelli, Italy.

Citation:
Silva F, Mendes C, D'Onofrio A, Campello MPC, Marques F, Pinheiro T, Gonçalves K, Figueiredo S, Gano L, Ravera M, Gabano E, Paulo A. Image-Guided Nanodelivery of Pt(IV) Prodrugs to GRP-Receptor Positive Tumors. Nanotheranostics 2023; 7(1):22-40. doi:10.7150/ntno.78807. https://www.ntno.org/v07p0022.htm
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Abstract

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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.

Keywords: gold nanoparticles, bombesin peptides, Pt(IV) prodrugs, 67Ga, prostate cancer


Citation styles

APA
Silva, F., Mendes, C., D'Onofrio, A., Campello, M.P.C., Marques, F., Pinheiro, T., Gonçalves, K., Figueiredo, S., Gano, L., Ravera, M., Gabano, E., Paulo, A. (2023). Image-Guided Nanodelivery of Pt(IV) Prodrugs to GRP-Receptor Positive Tumors. Nanotheranostics, 7(1), 22-40. https://doi.org/10.7150/ntno.78807.

ACS
Silva, F.; Mendes, C.; D'Onofrio, A.; Campello, M.P.C.; Marques, F.; Pinheiro, T.; Gonçalves, K.; Figueiredo, S.; Gano, L.; Ravera, M.; Gabano, E.; Paulo, A. Image-Guided Nanodelivery of Pt(IV) Prodrugs to GRP-Receptor Positive Tumors. Nanotheranostics 2023, 7 (1), 22-40. DOI: 10.7150/ntno.78807.

NLM
Silva F, Mendes C, D'Onofrio A, Campello MPC, Marques F, Pinheiro T, Gonçalves K, Figueiredo S, Gano L, Ravera M, Gabano E, Paulo A. Image-Guided Nanodelivery of Pt(IV) Prodrugs to GRP-Receptor Positive Tumors. Nanotheranostics 2023; 7(1):22-40. doi:10.7150/ntno.78807. https://www.ntno.org/v07p0022.htm

CSE
Silva F, Mendes C, D'Onofrio A, Campello MPC, Marques F, Pinheiro T, Gonçalves K, Figueiredo S, Gano L, Ravera M, Gabano E, Paulo A. 2023. Image-Guided Nanodelivery of Pt(IV) Prodrugs to GRP-Receptor Positive Tumors. Nanotheranostics. 7(1):22-40.

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