Ligand-functionalized inorganic nanoparticles are potential delivery vehicles for therapeutics that treat cancers and other diseases. Nanoparticles can bypass barriers that traditional drug delivery methods cannot and possess customizable surface ligands that are independent of the inorganic core.

But with only one Food and Drug Administration-approved inorganic nanoparticle on the market besides iron supplements, the use of therapeutic nanoparticles is underdeveloped. Often, potential therapeutic nanoparticles have low efficacy or low biocompatibility. These problems could be fixed by engineering the chemistry of the surface ligands to increase selectivity to their targets and reduce immune activation. There is still, however, a lack of understanding of how surface ligands interact with different classes of biomolecules, including nucleic acids, membranes and proteins, that remains a hurdle to improving ligand design.

To help guide ligand design, Manning et al. analyzed recent studies on nanoparticle interactions with biomolecules. The authors looked for commonalities to develop rules for nanoparticle design. Analyzing experimental and computational studies, they found that the charge and hydrophobicity of ligands is crucial to nanoparticle biocompatibility and efficiency. They also noted that more complex ligands, like those with more branches, could be more efficient, but aren’t sure why. Ligand length and flexibility influence nanoparticle properties as well, but how still remains unanswered.

The authors hope others in the field will help answer open questions like these using all available tools, including high-throughput synthesis, characterization, simulations and machine learning. Manning said that the number of possible ligand designs is massive, so nanoparticle designers need a playbook that allows them to be more strategic during synthesis. Creating this playbook requires understanding nanoparticle interactions with biomolecules, which will help turn potential nanoparticle therapies into realities.

Source: “Progress in ligand design for monolayer-protected nanoparticles for nanobio interfaces,” by Matthew D. Manning, Albert L. Kwansa, Thomas Oweida, James S. Peerless, Abhishek Singh, and Yaroslava G. Yingling, Biointerphases (2018). The article can be accessed at https://doi.org/10.1063/1.5044381.