How does one manipulate the behavior of nano particles?

Hello,

I'm talking about my research the interaction and application of silver nanoparticles with protein in syringes used in biomedicaments:

Introducition:

The understanding of the intrinsic physical and chemical properties of nanoparticles (NPs), along with their capability to interact with biomolecules, has derived in the development of several promising applications in biomedicine and biotechnology. For this purpose, unique properties of metallic NPs, such as the optical responses originated from the excitation of surface plasmon resonance (SPR) (i.e., the collective oscillation of surface electrons) are assessed. This characteristic resonance is dependent on the size, shape and spatial arrangement of NPs, and strongly sensitive to the surrounding medium. In effect, when another biomolecule interacts with the surface of NPs there is a modification in the adjacent chemical and physical environment (i.e., the bio-nano interface), leading to specific absorption and scattering responses that can be used to monitor this interaction. Particularly, it is recognized that proteins can be adsorbed non-specifically onto NPs establishing a protein corona with distinctive properties. By seizing this knowledge, NPs can be used for protein sensing in developing fields like medical diagnostics and therapeutics. For instance, protein-based therapeutics demand delivery container closure systems that can allow a safe and efficient dosing. However, depending on the physicochemical nature of the protein (i.e., mass, charge, shape and hydrodynamic volume) an affinity towards a particular surface will always exist at a greater or lesser degree. This inherent property can result in the loss of active pharmaceutical ingredient (API) through adsorption on the components that are in direct contact with the dosage form (i.e., primary packaging), increasing the likelihood to undergo the formation of aggregates, which relate to the occurrence of adverse events like vascular occlusion and immunogenicity. Hence, the intra-batch, inter-batch and inter-brand assessment of the primary container (or their components) characteristics in terms of its compatibility with the protein can be used to define the suitability of use. Further, this evaluation can be useful to outline a quality attribute aimed to avoid potential impacts on the safety and efficacy of drug products. In this work, a monoclonal antibody (mAb) and a synthetic copolymer (SC) were used as protein models with increasing therapeutic interest. The investigation of the structural changes of these proteins upon contact with silver nanoparticles (AgNPs) was conducted through microscopy, colorimetric, fluorescence, dichroic, and scattering techniques. Further, we propose a methodology to determine the occurrence of protein adsorption onto different commercially available containers using AgNPs as protein sensor. Particularly, the present study considered siliconized-glass syringes as the container for model proteins.

Abstract

Silver nanoparticles (AgNPs) have been well characterized for distinct biomedical and biopharmaceutical applications including protein sensing, targeting and delivery, underlying the primary principles of protein-nanoparticle interactions. As first step, transmission electron microscopy in combination with colorimetric, fluorescent, dichroic and scattering responses were used to characterize protein-AgNPs complexes using two therapeutic molecules as models: a monoclonal antibody (mAb) and a synthetic copolymer (SC). Upon interaction, a protein corona was formed around AgNPs with the consequent modification of the surface plasmon resonance of AgNPs. For both proteins, the reduction of the fluorescence lifetime and the increase of the hydrodynamic radii confirmed their aggregation over the AgNPs. Circular dichroism analysis indicated a relaxation of the peptide bonds within the mAb, whereas for the SC a rigidification of its structure was implied, resulting in the enhancement of its α-helix signal due to the reduced dichroic random coil contribution. Giving the understanding of protein-AgNPs complexation effects, AgNPs capability to interact with proteins was used to conduct the compatibility assessment between the protein models and siliconized-glass syringes. Differential adsorption in the intra-batch, inter-batch and inter-brand evaluation of siliconized-glass syringes was determined visually and by changes in the UV-vis absorption of AgNPs surface plasmons. Singular behaviors were exhibited at different protein concentrations, providing evidence of the level of adsorption from 10 ng mL-1 to 20 or 50 mg mL-1 for the SC and the mAb, respectively. These findings allowed the characterization of the relationship between therapeutic proteins with AgNPs. Therefore, by applying this knowledge, it is possible to assist the case-by-case evaluation of primary 3 containers or their components in terms of their propensity to adsorb protein, as a quality attribute.

We appreciate your attention in this matter.
Kind regards,
INA. Diego Méndez

Hi Daniel.

Atoms and molecules can be manipulated with tools such as an Atomic Force Microscope (AFM) or a Scanning Tunneling Microscope (STM). IBM has done some cool demos that you can find online: https://www.ibm.com/blogs/research/2013/05/how-to-move-an-atom/ . The basic principle of manipulation is that you can use a very sharp tip (as sharp as a few atoms thick) in conjunction with a charge to either attract or repel atoms or molecules.

As you can imagine it would be unpractical to manage billions or trillions of atoms one by one. So, in order to make real world applications, we rely on chemical and physical processes that can either manufacture or place nanoparticles where they are needed, or at least close enough. An example of a chemical process is Chemical Vapor Deposition (CVD) and an example of a physical process is milling and Physical Vapor Deposition (PVD).

Hope these examples help.

Best,

Fernando.

Hello,

Speaking from experience with nanoparticles, the biggest impact on NP (Nano Particle) behavior depends on the size of the NPs.

Various elements will require different techniques to change the size of the materials.

For example, while I was working at Southwest Research Institute, we used a process called Bead Milling to grind nanoparicle minerals to a smaller size than provided. This allowed us to change particle behavior for emulsion based formulas. These materials were softer elements, and so techniques would be less extreme than other methods that I have seen.

Another example would be something such as gold. However, gold would need a different approach.

We used autoclaving techniques to adjust the particle size of gold. With different yields of Gold sizes, we observed different colors of gold, each with variations in conductivity. So for a material such as gold, you can end up with Blue, green red, etc colors. An application for a technique like this could allow for broader sunlight absorption properties in solar panels.

The tricky part would be finding the right balance between material cost and the efficiency of the elements involved. This principle ultimately will prove to be important in many aspects of Nanotechnology.

There are plenty of other examples out there but each will be specific to a certain application. We know that Nanotechnology is a versatile field; and so as you begin to narrow down your interests for research, it will also help you decide which methods to dive deeper into your personal studies.