Targeting 3D Bladder Cancer Spheroids with Urease-Powered Nanomotors

Abstract

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.

Recent Advances in Nano‐ and Micromotors

“…As a result, the HeLa cell viability was >80% and ≈5% when exposed to dox‐loaded nanomotors using no urea and 100 × 10 −3 m urea, respectively. Following on, they developed antibody‐functionalized urease‐PEG powered nanomotors with the aim to eventually target bladder cancer . These nanomotors explored larger areas due to their locomotion compared to passively diffusing controls.…”

“…Following on, they developed antibody-functionalized urease-PEG powered nanomotors with the aim to eventually target bladder cancer. [93] These nanomotors explored larger areas due to their locomotion compared to passively diffusing controls. In the former case, binding between the specific anti fibroblast growth factor receptor 3 (FGFR3)-antibody and the FGFR3 antigens presented in the cancer spheroids was more likely to happen, and as a consequence better fibroblasts growth inhibition was anticipated because of the blocking of cell proliferation.…”

Monitoring the collective behavior of enzymatic nanomotors in vitro and in vivo by PET-CT

“…Self-propelled particles hold potential to overcome the biological barriers that limit current cancer nanomedicines, where only 0.7% of the administered dose reaches the target in vivo. (1) In this regard, micro-and nanomotors have demonstrated enhanced targeting properties (2)(3)(4)(5) and superior drug delivery efficiency compared to passive particles. (6)(7)(8)(9) Additionally, they outperform traditional nanoparticles in terms of penetration into biological material, such as mucus, (10)(11)(12)(13) cells (14)(15)(16) or spheroids.…”

“…(6)(7)(8)(9) Additionally, they outperform traditional nanoparticles in terms of penetration into biological material, such as mucus, (10)(11)(12)(13) cells (14)(15)(16) or spheroids. (4,17) Particularly, using enzymes as biocatalysts is emerging as an elegant approach when designing self-propelled particles, due Nanomotors were prepared by synthesizing mesoporous silica nanoparticles (MSNPs) using a modification of the Stöber method (see experimental section for details), (46) and their surface was modified with amine groups by attaching aminopropyltriethoxysilane 7 temperature) of the nanomotors with the prosthetic group. Radioiodination was achieved by direct absorption of 124 I on AuNPs on the nanomotors.…”

“…The self-propulsion of urease-modified micro-/nanomotors (4,(52)(53)(54) is caused the asymmetric release of ionic species from the particles to the solution (55) which stems from the catalytic decomposition of urea into carbon dioxide and ammonia. Despite the recent advances in the field, enzyme nanomotors have been only studied from single particle to a few particles case, being their collective swarming behaviour not investigated to date.…”