Targeting 3D Bladder Cancer Spheroids with Urease-Powered Nanomotors

Cancer is one of the main causes of death around the world, lacking efficient clinical treatments that generally present severe side effects. In recent years, various nanosystems have been explored to specifically target tumor tissues, enhancing the efficacy of cancer treatment and minimizing the si...

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Bibliographic Details
Published in:ACS nano 2019-01, Vol.13 (1), p.429-439
Main Authors: Hortelão, Ana C, Carrascosa, Rafael, Murillo-Cremaes, Nerea, Patiño, Tania, Sánchez, Samuel
Format: Article
Language:English
Subjects:
Antibodies - immunology
Cells, Cultured
Humans
Motion
Nanoparticles - chemistry
Nanoparticles - metabolism
Polyethylene Glycols - chemistry
Receptor, Fibroblast Growth Factor, Type 3 - immunology
Silicon Dioxide - chemistry
Spheroids, Cellular - metabolism
Tumor Cells, Cultured
Urea - metabolism
Urease - chemistry
Urease - metabolism
Urinary Bladder Neoplasms - pathology
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Summary:Cancer is one of the main causes of death around the world, lacking efficient clinical treatments that generally present severe side effects. In recent years, various nanosystems have been explored to specifically target tumor tissues, enhancing the efficacy of cancer treatment and minimizing the side effects. In particular, bladder cancer is the ninth most common cancer worldwide and presents a high survival rate but serious recurrence levels, demanding an improvement in the existent therapies. Here, we present urease-powered nanomotors based on mesoporous silica nanoparticles that contain both polyethylene glycol and anti-FGFR3 antibody on their outer surface to target bladder cancer cells in the form of 3D spheroids. The autonomous motion is promoted by urea, which acts as fuel and is inherently present at high concentrations in the bladder. Antibody-modified nanomotors were able to swim in both simulated and real urine, showing a substrate-dependent enhanced diffusion. The internalization efficiency of the antibody-modified nanomotors into the spheroids in the presence of urea was significantly higher compared with antibody-modified passive particles or bare nanomotors. Furthermore, targeted nanomotors resulted in a higher suppression of spheroid proliferation compared with bare nanomotors, which could arise from the local ammonia production and the therapeutic effect of anti-FGFR3. These results hold significant potential for the development of improved targeted cancer therapy and diagnostics using biocompatible nanomotors.
ISSN:1936-0851
1936-086X
DOI:10.1021/acsnano.8b06610