A new study by Carina Crucho and Pedro Viana Baptista, from the Nanomedicine Lab at UCIBIO NOVA FCT, introduces tangible 3D models to optimize nanoparticle design for medicine, imaging, and diagnostics. The research works have published a breakthrough study in ACS Nano, a leading journal in the field of nanotechnology and materials science. The paper, titled "Making Room at the Nanoscale: A Tangible Perspective on Surface Crowding and Molecular Design," addresses a fundamental challenge in nanomedicine: understanding exactly how much physical space is available on a nanoparticle's surface.
The challenge: overcrowding at the nanoscale
Designing functional nanoparticles requires more than just controlling their size and shape; it demands high spatial awareness at the molecular level. While nanoparticles are essential tools for targeted medicine and diagnostics, their surface space is strictly limited.
The research team explored how the addition of different molecules, such as polymers, targeting antibodies, or dyes, quickly leads to competition for space. If too many molecules are added, they experience steric hindrance, effectively blocking each other and reducing the overall performance and efficacy of the nanoparticle.
Making the invisible tangible
To tackle this problem, the researchers shifted away from abstract concepts of ligand density and created something highly tangible. They built scaled physical models and 3D-printed versions of nanoparticles to translate microscopic features into visible dimensions. Guided by real molecular dimensions reported in scientific literature, these models allow researchers to compare how the exact same molecules behave on larger versus smaller surfaces.
"Our paper in ACS Nano explores a simple but important question: how much space is really available on the surface of a nanoparticle?" explains Carina Crucho, researcher at UCIBIO-NOVA FCT. "We built physical and 3D-printed models to make nanoscale ‘crowding’ visible. When too many molecules are added to a nanoparticle, they can block each other and reduce performance. By making the invisible visible, this work helps researchers design better nanoparticles for medicine, imaging, and diagnostics, and makes nanoscience easier to understand."
Bridging Nanoscience and Intuitive Design
Beyond illustrating complex physical chemistry concepts, such as polymer brush regimes and ligand density thresholds, this approach bridges quantitative nanoscience with intuitive visualization.
Pedro Viana Baptista, leader of the Nanomedicine Lab at UCIBIO-NOVA FCT, highlights the broader impact of this innovative approach: "This work helps researchers better understand and design nanoparticles. By making nanoscale crowding visible and intuitive, it supports smarter experimental design choices and fosters clearer communication across different scientific fields."
Ultimately, this study serves not only as a powerful tool to support rigorous experimental design but also as a highly effective resource for scientific education, outreach, and interdisciplinary collaboration.
Read the full paper in ACS Nano here:
Images from the article:
"Scaled nanoparticle models. (A) Handcrafted version built from simple materials to represent biomolecular components at scale. See Figure S1 for material–component mapping. (B) 3D-printed version designed for reproducibility and broader dissemination. Scale bar: 4 cm. Photo credit: João Lima/NOVA FCT."
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