Super-resolution imaging of self-propelled nanoparticles for nanomedicine

Nanoscopy for nanomedicine group · Lorenzo Albertazzi  //  Smart nano-bio-devices · Samuel Sánchez

Research project

Nanomaterials hold a great promise for a variety of biomedical applications, in which is crucial to understand the behavior of nanomaterials in the complex biological environment.

Among the different nanocarriers, nanomotors have emerged as a powerful alternative to passive nanoparticles. Nanomotors are artificial systems able to self-propel thanks to the enzymatic conversion of chemical energy into an active motion.

However, nanomotors will need to overcome biological barriers to reach their target, which will include motion in fluids such as blood, interstitial and synovial fluids or the extracellular matrix. How do nanomotors behave in those fluids? Which is the best shape and size to move in viscous fluids? Which enzyme on the nanomotor generates more power?

In the case of blood, not only it is a crowded media, but it also contains many sticky proteins able to attach on nanoparticles surfaces (i.e. protein corona) and prevent the envisioned use of the nanomaterials. How protein corona affects the movement of nanomotors has still not been studied, and it is crucial for its efficient application.

Thus, the project will focus on developing nanomotors able to move in biological fluids and circumvent protein corona formation. For doing so a library of nanomotors of different architectures, sizes and shapes will be synthesized. Also, different enzyme types and different quantity and distribution of enzyme on the nanomotors surface will be prepared.

Its motion in in biological fluids will be evaluated by optical tracking and dynamic light scattering (see Figure 1).

Figure 1. Urease-powered nanomotor: motion as a function of urea concentration

Enzyme quantity and distribution on nanomotors is challenging to study due to the diffraction limit in conventional optical microscopes. However, recently super resolution microscopy (SRM) has emerged as a very powerful tool able to surpass the diffraction limit and reach the nanoscale. Thanks to this technique we could observe urease quantity and distribution on micromotors (see Figure 2).

Figure 2. Urease-powered micromotor visualized by super resolution microscopy. Localization and 3D distribution of the enzyme on the motor surface.

The next step is to do it on the nanomotors library, and use SRM also to study protein corona formation, i.e. to visualize the interactions with blood components. Correlation of the data obtained by SRM with the motion data will allow to establish the best motor.

The rational design of nanomotors will strongly impact the field of nanomaterials providing a valuable tool for the whole drug delivery community.

Job position

The student will be involved in:

  • Synthesising a library of nanomotors: from silica nanoparticles synthesis to surface functionalization with enzymes.
  • Different geometries, sizes, enzyme type, quantity and distribution will be explored and characterised.
  • Nanoparticles modification with dyes for super resolution imaging.
  • Learning the use of super resolution microscopy to characterise the library of nanomotors.
  • Studying protein corona formation on nanomotors by super resolution microscopy.
  • Evaluating nanomotors motion in biological fluids and before and after protein corona formation by optical tracking and dynamic light scattering.
  • Nanomotor on-demand design optimization: the results of the nanomotors library will conclude which is the most efficient nanomotor for each biological environment, thus allowing and constituting drug delivery system for cancer therapy.

The project is between the Nanoscopy for Nanomedicine group and the Smart nano-bio-devices group, both at IBEC. Both groups are devoted to the efficient design of nanomaterials for nanomedicine and have been collaborating for the past 3 years. The role of each group in the project is clearly established to ensure fruitful and outstanding results in the field.

The project is in the framework of several European consortia and collaborations and visiting period abroad are envisioned.