Urease-powered nanobots for radionuclide bladder cancer therapy

Cristina Simó; Meritxell Serra-Casablancas; Ana C. Hortelao; Valerio Di Carlo; Sandra Guallar-Garrido; Sandra Plaza-García; Rosa Maria Rabanal; Pedro Ramos-Cabrer; Balbino Yagüe; Laura Aguado; Lídia Bardia; Sébastien Tosi; Vanessa Gómez-Vallejo; Abraham Martín; Tania Patiño; Esther Julián; Julien Colombelli; Jordi Llop; Samuel Sánchez

doi:10.1038/s41565-023-01577-y

Urease-powered nanobots for radionuclide bladder cancer therapy

Cristina Simó, Meritxell Serra-Casablancas, Ana C. Hortelao, Valerio Di Carlo, Sandra Guallar-Garrido, Sandra Plaza-García, Rosa Maria Rabanal, Pedro Ramos-Cabrer, Balbino Yagüe, Laura Aguado, Lídia Bardia, Sébastien Tosi, Vanessa Gómez-Vallejo, Abraham Martín, Tania Patiño, Esther Julián, Julien Colombelli (Corresponding author), Jordi Llop (Corresponding author), Samuel Sánchez (Corresponding author)

Onderzoeksoutput: Bijdrage aan tijdschrift › Tijdschriftartikel › Academic › peer review

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Bladder cancer treatment via intravesical drug administration achieves reasonable survival rates but suffers from low therapeutic efficacy. To address the latter, self-propelled nanoparticles or nanobots have been proposed, taking advantage of their enhanced diffusion and mixing capabilities in urine when compared with conventional drugs or passive nanoparticles. However, the translational capabilities of nanobots in treating bladder cancer are underexplored. Here, we tested radiolabelled mesoporous silica-based urease-powered nanobots in an orthotopic mouse model of bladder cancer. In vivo and ex vivo results demonstrated enhanced nanobot accumulation at the tumour site, with an eightfold increase revealed by positron emission tomography in vivo. Label-free optical contrast based on polarization-dependent scattered light-sheet microscopy of cleared bladders confirmed tumour penetration by nanobots ex vivo. Treating tumour-bearing mice with intravesically administered radio-iodinated nanobots for radionuclide therapy resulted in a tumour size reduction of about 90%, positioning nanobots as efficient delivery nanosystems for bladder cancer therapy.

Originele taal-2	Engels
Pagina's (van-tot)	554-564
Aantal pagina's	11
Tijdschrift	Nature Nanotechnology
Volume	19
Nummer van het tijdschrift	4
Vroegere onlinedatum	15 jan. 2024
DOI's	https://doi.org/10.1038/s41565-023-01577-y
Status	Gepubliceerd - apr. 2024

Financiering

The research leading to these results has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement 866348, i-NanoSwarms) (S.S.). The IBEC team wishes to thank the CERCA programme of the Generalitat de Catalunya, the Secretaria d’Universitats i Recerca del Departament d’Empresa i Coneixement de la Generalitat de Catalunya through project 2021-SGR-01606, and the ‘Centro de Excelencia Severo Ochoa’, funded by Agencia Estatal de Investigación (CEX2018-000789-S), for funding. S.S., J.L., E.J., M.S-C. and V.D.C. acknowledge ‘La Caixa’ Foundation under the grant agreement LCF/PR/HR21/52410022 for project ‘BLADDEBOTS’. J.L., V.G.-V. and C.S. thank MICINN (PID2020-117656RB-I00) for financial support. The ReDIB ICTS infrastructure at CIC biomaGUNE was used for radiolabelling and in vivo imaging. S.G.-G. and E.J. thank the Ministerio de Ciencia, Innovación y Universidades (PID2021-122331OB-I00) and the Generalitat de Catalunya (2021-SGR-0092). We thank A. Ruiz de Angulo Dorronsoro, A. Punzano and H. Jorge for technical support. We thank the Smart Nano-bio-devices group for proofreading the manuscript. Editorial assistance, in the form of language editing and correction, was provided by XpertScientific Editing and Consulting Services.

Financiers	Financiernummer
Centro de Excelencia Severo Ochoa
Horizon 2020 Framework Programme	866348
European Research Council
Generalitat de Catalunya	2021-SGR-01606
Ministerio de Ciencia e Innovación	PID2020-117656RB-I00
Agencia Estatal de Investigación	CEX2018-000789-S, LCF/PR/HR21/52410022

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Simó, C., Serra-Casablancas, M., Hortelao, A. C., Di Carlo, V., Guallar-Garrido, S., Plaza-García, S., Rabanal, R. M., Ramos-Cabrer, P., Yagüe, B., Aguado, L., Bardia, L., Tosi, S., Gómez-Vallejo, V., Martín, A., Patiño, T., Julián, E., Colombelli, J., Llop, J., & Sánchez, S. (2024). Urease-powered nanobots for radionuclide bladder cancer therapy. Nature Nanotechnology, 19(4), 554-564. https://doi.org/10.1038/s41565-023-01577-y

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abstract = "Bladder cancer treatment via intravesical drug administration achieves reasonable survival rates but suffers from low therapeutic efficacy. To address the latter, self-propelled nanoparticles or nanobots have been proposed, taking advantage of their enhanced diffusion and mixing capabilities in urine when compared with conventional drugs or passive nanoparticles. However, the translational capabilities of nanobots in treating bladder cancer are underexplored. Here, we tested radiolabelled mesoporous silica-based urease-powered nanobots in an orthotopic mouse model of bladder cancer. In vivo and ex vivo results demonstrated enhanced nanobot accumulation at the tumour site, with an eightfold increase revealed by positron emission tomography in vivo. Label-free optical contrast based on polarization-dependent scattered light-sheet microscopy of cleared bladders confirmed tumour penetration by nanobots ex vivo. Treating tumour-bearing mice with intravesically administered radio-iodinated nanobots for radionuclide therapy resulted in a tumour size reduction of about 90%, positioning nanobots as efficient delivery nanosystems for bladder cancer therapy.",

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Simó, C, Serra-Casablancas, M, Hortelao, AC, Di Carlo, V, Guallar-Garrido, S, Plaza-García, S, Rabanal, RM, Ramos-Cabrer, P, Yagüe, B, Aguado, L, Bardia, L, Tosi, S, Gómez-Vallejo, V, Martín, A, Patiño, T, Julián, E, Colombelli, J, Llop, J & Sánchez, S 2024, 'Urease-powered nanobots for radionuclide bladder cancer therapy', Nature Nanotechnology, vol. 19, nr. 4, blz. 554-564. https://doi.org/10.1038/s41565-023-01577-y

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AU - Hortelao, Ana C.

AU - Di Carlo, Valerio

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AU - Rabanal, Rosa Maria

AU - Ramos-Cabrer, Pedro

AU - Yagüe, Balbino

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AU - Tosi, Sébastien

AU - Gómez-Vallejo, Vanessa

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AB - Bladder cancer treatment via intravesical drug administration achieves reasonable survival rates but suffers from low therapeutic efficacy. To address the latter, self-propelled nanoparticles or nanobots have been proposed, taking advantage of their enhanced diffusion and mixing capabilities in urine when compared with conventional drugs or passive nanoparticles. However, the translational capabilities of nanobots in treating bladder cancer are underexplored. Here, we tested radiolabelled mesoporous silica-based urease-powered nanobots in an orthotopic mouse model of bladder cancer. In vivo and ex vivo results demonstrated enhanced nanobot accumulation at the tumour site, with an eightfold increase revealed by positron emission tomography in vivo. Label-free optical contrast based on polarization-dependent scattered light-sheet microscopy of cleared bladders confirmed tumour penetration by nanobots ex vivo. Treating tumour-bearing mice with intravesically administered radio-iodinated nanobots for radionuclide therapy resulted in a tumour size reduction of about 90%, positioning nanobots as efficient delivery nanosystems for bladder cancer therapy.

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Urease-powered nanobots for radionuclide bladder cancer therapy

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