Bio- interactions of nanomaterials Flashcards
Biodegradable
A substance that can breakdown naturally into harmless products through the action of living things (Being decomposed by bacteria or other living organisms). For biomedical applications it is obligatory to use bio-degradable or at least biocompatible polymers as building block. Examples include: Polycaprolactone (PCL) or Poly(lactic acid) (PLA) Oligo- and polypeptides.
Biocompatible
A substance that is not harmful/toxic to living tissue and does not interfere with natural processes in living tissue.
Opsonins
An antibody or substance that binds to foreign cells and makes them (the foreign cells) more vulnerable to phagocytosis. Phagocytosis is a process where a phagocyte captures a virus or infected cell and breaks it down.
Stealth behavior
Stealth behavior is the behavior in which the liposome is not detected by the RES by the PEG mantle, which results in a prolonged circulation time. Always neutral or negatively charged, positively charged cells will be taken up by macrophages.
Effect of polymer glass transition
Amorphous polymers have a glass transition temperature (Tg) which is the transition from glassy to rubbery state.
Below Tg: polymers have lower mobility: they are hard and brittle (similar to glass)
Above Tg: polymers have higher mobility: they are flexible and softer (similar to rubber)
Factors that influence Tg:
* Molecular weight (higher Mw lowers chain end concentration, yielding higher Tg)
* Molecular structure (inflexible side groups reduce mobility and increase Tg)
* Chemical cross-linking (more cross-links reduces mobility and increases Tg)
* Polar groups (polar groups cause forces between molecules, increasing Tg)
Effect of pKa of polymer side groups
Polymer side groups with low pKa have the tendency to become protonated in low pH solution. Therefore, this can be used to (dis)assemble polymersomes upon pH change. Important use as drug release mechanism Fe zwitteronic or ionizable blocks
Peptosome
A peptosome is a type of liposome, which is a spherical vesicle made up of a lipid bilayer. However, unlike a traditional liposome, a peptosome also contains peptides (short chains of amino acids) within its lipid bilayer.
Reticuloendothelial System (RES)
The Reticuloendothelial System (RES) is a network of cells and organs in the body that helps in the defense against foreign substances, such as bacteria and viruses. The system consists of specialized cells called macrophages, which are found in various organs throughout the body, including the liver, spleen, and lymph nodes.
Macrophages play a crucial role in this process, as they are able to recognize and bind to these foreign substances through specialized receptors on their cell surface. Once bound, the macrophages will engulf the foreign particles in a process called phagocytosis. The engulfed particles are then broken down by enzymes within the macrophage and eliminated from the body.
Use of lower critical solution temperature
Property of polymers where they go from soluble state to insoluble. Above this temp. polymersomes form, below they dissolve. This happens because of self-assembly of the hydrophobic parts, creating a membrane. ENTROPY OF WATER
Blood half-life of polymersomes vs. liposomes
Blood half-life is the time it takes the blood plasma concentration of liposomes/polymersomes to halve. Polymersomes are more robust compared to liposomes, this will lead to a longer circulation time. For the liposomes, the blood half life depends on the size of the liposome, which can be seen the figure below.
Alternatives for PEG to induce stealth behavior
- Zwitterionic polymer PMPC –> found to reduce the absorption of opsonins.
- pHPMA and Oligosaccharides (e.g. cyclodextrin) –> both show possibility, have been investigated as polymer-conjugate therapeutics.
- Poly(oxazoline) conjugates –> shows prolonged circulation times.
How does size matter?
- Blood circulation time, Small is longer circulation time (not too small!!), Large is shorter circulation time.
- RES recognition -> Imuun system -> Phagocytic cells in fixed cells -> Clearance of particles.
- Biodistribution.
- Mechanism of cell uptake is different.
EPR effect
Enhanced Permeability and Retention effect (EPR). Molecules, such as liposomes and nanoparticles tend to accumulate in tumor tissue more than they do in normal tissue. Not every tumor will show this effect. The EPR depends on the ratio of the leaky vessels and the lymphatic pressure.
Shape effect worm vs. spherica
Worm-like micelles have longer blood circulation time than spherical particles like liposomes and polymersomes. Micelles or worm-like micelles can’t deliver hydrophilic compounds, but there have been worm-like polymersomes observed that can encapsulate hydrophilic compounds. Worm-like shaped particles flow with less resistance in the bloodstream compared to spherical particles.
Effect of surface charge as in red blood cells
- Red blood cells have an overall negative charge.
- Negative particles accumulate in liver
- Negative charged particles have a lower half time than neutral particles
What to consider upon putting surface functionalities on polymeric particle
- The charge
- Size of the particle
- Circulation time
- Size of the PEG
- The uptake of the cell
Cell penetrating peptides
A cell penetrating peptide (CPP) is a short peptide sequence, typically consisting of 10-30 amino acids, that has the ability to pass through the cell membrane and enter the cytoplasm or nucleus of a cell. These peptides are able to bind to and cross the cell membrane through various mechanisms, such as direct membrane translocation, endocytosis, or receptor-mediated uptake.
Sponge effect
An endosome can well up and burst due to an imbalance of the charge. The proton sponge effect is a phenomenon in which a compound or molecule has a high affinity for protons (positively charged hydrogen ions) and can readily accept them. This results in the compound becoming highly charged and producing a strong basic environment. This effect is commonly observed in a class of compounds known as quaternary ammonium salts, which have multiple positive charges and can act as “proton sponges” by readily accepting protons from the surrounding environment. This effect has various applications in chemistry, including in the design of catalysts and pH indicators.
How about getting stuck?
- Glomerular filtration barrier in the kidneys
- Particles bigger then 120 nm are likely to accumulate in the liver and spleen
Methods to measure biodistributions (radio labeling, NIR)
- Radiolabeling is a form of isotopic labeling and is performed by scientists to track a molecule’s journey through a cell or chemical reaction. All elements can consist of at least 2 isotopes with a different number of neutrons in the nucleus. The isotopes are easy to trace but do not change the behaviour of the molecule. There are several compounds that can be used for radio labeling. Some of the most commonly used radiolabeled compounds today are carbon-14 (14C labeling), tritium (3H) and sulfur-35 (35S).
- Near infrared Spectroscopy and Imaging (NIRS) uses near-infrared light between 650 and 950 nm to measure the concentration and oxygenation of hemoglobin in the brain, muscles and other tissues in a non-invasive (i.e. research that does not require the insertion of equipment into the body) and is used, for example, to detect changes due to brain activity, detect injury or illness. In brain research, functional magnetic resonance imaging (fMRI) complements by providing measurements of both oxygenated and oxygenated hemoglobin concentrations and by enabling studies in populations of subjects with experimental paradigms that are not suitable for fMRI.
Biodistribution of nanoparticles
Refers to the study of the distribution of nanoparticles in living organisms.
Effect of size, shape and Zeta potential on cell uptake
Size: Smaller particles have a higher surface area to volume ratio, which may increase the likelihood of interaction with cells. This can lead to a higher uptake efficiency as more cells can come into contact with the material. Additionally, smaller particles may be able to enter cells through endocytosis or other mechanisms, making them more easily internalized.
Shape: The shape of nanoparticles can also play a role in their targeting ability. Some shapes, such as rod-shaped nanoparticles, have been found to have better targeting abilities compared to spherical ones. This is because their elongated shape allows them to better interact with specific receptors on the cell surface, increasing their chances of being taken up by the target cells.
Zeta potential: The zeta potential of a material refers to its surface charge and can also influence cell uptake. Cells have a slightly negative surface charge, so materials with a positive zeta potential may have a higher affinity for cells. This can increase the likelihood of interaction and internalization by cells. However, excessively high positive or negative zeta potentials can also lead to repulsion between cells and the material, reducing the uptake efficiency.
