Scientists at Arizona State University have discovered that the way nanoparticles interact with water determines their behavior within the human body, providing a new thermodynamic framework that could lead to more effective nanomedicine.
researchers arizona state university identified fundamental scientific principles that can determine how engineering is done nanoparticles operates within the human body. the study Unlocking the potential of nanomedicine could lead to safer and more powerful treatments.
In the study, the researchers directly measured how water interacts with the coated nanoparticles and how those interactions affect the nanoparticles’ biological performance.
Why is water important?
“Water is necessary for all life,” said the study’s lead author, Alexandra Nabrodsky, Regents Professor in the Department of Molecular Sciences and director of the Center for Space Materials at Arizona State University. “And in medicine, it is the first molecule to interact with a nanoparticle surface in a biological environment. By directly measuring the adsorption energy of water, we can quantify the interaction potential of the nanoparticle surface and more accurately predict how the nanoparticle surface will behave in the body.”
Despite decades of research, nanomedicine has struggled to provide a new generation of safer and more effective treatments.
Despite decades of research, nanomedicine has struggled to provide a new generation of safer and more effective treatments. The human body has many barriers that make it difficult to ensure that drugs reach the right target at the right time. For example, traditional chemotherapy attempts to destroy tumors while often spreading toxic compounds throughout the body.
To address this, scientists have developed “Trojan horse” strategies that envelop drugs inside protective nanoparticle shells. Upon entering the body, these particles are surrounded by water and biomolecules, forming complex structures that determine the particle’s stability, circulation time, immune response, and uptake by cells.
Until now, researchers had not directly measured the adsorption energy of water on magnetic nanoparticles coated with biomolecules.
Get to the heart of the matter
The researchers studied magnetite nanoparticles coated with three representative biomolecules: the protein bovine serum albumin, the polysaccharide potato starch, and the fatty acid lauric acid. They used a sensitive calorimetry-gas adsorption system to measure how water interacted with each coating and compared the results to uncoated magnetite and free biomolecules.
Their results revealed that each surface coating dramatically changes the hydration behavior and potential for biological interactions.
uneven protein layer
Nanoparticles coated with bovine serum albumin, commonly used as a model for drug delivery studies, showed the strongest initial interaction with water. The coating created strong binding sites on the particle surface. However, the total water uptake is lower than the free protein uptake, suggesting that the magnetite coverage is incomplete and partially exposed.
Nanoparticles coated with bovine serum albumin, commonly used as a model for drug delivery studies, showed the strongest initial interaction with water.
“The protein coating increases the potential for surface interactions in the nanocomplex,” says Kristina Lilova, assistant professor at Arizona State University’s Center for Space Materials. “However, the presence of exposed magnetite regions may introduce heterogeneity and promote protein corona formation and immune recognition.”
Such plaques may facilitate the adsorption of opsonins, proteins that mark foreign bodies for immune clearance, reducing circulation time.
starch shield
In contrast, starch-coated nanoparticles exhibited a large hydrophilic surface area but weaker interaction potential. Starch formed a dense shell around the magnetite core, restricting the access of water molecules.
“The weaker interaction potential of the starch coating and its relatively large hydrophilic surface area suggest a more dynamic and reversible binding,” Rylova said. “This could be beneficial in drug delivery where mobility along cell membranes and reduced cytotoxicity are desirable.”
fatty acid coating
The most surprising discovery concerned lauric acid. Free lauric acid does not adsorb water, but when combined with magnetite, it reorganizes into a partial bilayer structure that strongly interacts with water.
“The fatty acids rearrange themselves into a partial bilayer that has very strong hydrophilic properties,” says Rylova. “That structure may increase stability and reduce immune activation compared to more hydrophobic surfaces.”
Aiming for rational nanomedicine
The researchers established hydration enthalpy as a key thermodynamic parameter governing surface hydrophilicity, heterogeneity, and biological interactions across all three coatings.
Our findings demonstrate that surface functionalization not only changes the chemistry but also fundamentally alters the thermodynamic landscape of the nanobiointerface.
“Our results show that surface functionalization not only changes the chemistry, but also fundamentally changes the thermodynamic landscape of the nanobiointerface,” Rylova said. “Understanding primary hydration energetics allows us to rationally design nanocarriers with customized stability, immune interactions, and drug delivery behavior.”
It is hoped that these findings can inform the future design of targeted drug delivery systems, contrast agents, and cancer treatments.
“This work provides a thermodynamic basis for designing nanocarriers with predictable biological reactivity, which brings us one step closer to truly rational nanomedicine,” said Nabrodsky.