Nanoparticle Dynamics: Exposure, Absorption, and Elimination

Nanoparticles: Uptake and Fate

Learning Outcomes

  • Identify situations where humans are exposed to nanoparticles.
  • Discuss how nanoparticles traverse natural barriers in the human body.
  • Describe clearance mechanisms for nanoparticles of varying sizes.

Definition of Nanoparticles

  • Nanoparticles are objects, either natural or synthetic, with dimensions in the sub-micrometer range.
  • They can be made up of one or multiple materials.

Size Comparison

  • Illustration comparing a cell to a house, and a 100nm particle to a marble. This highlights the scale difference, where If a cell was the size of a house, a 100 nanometer particle would be the size of a marble.

Exposure to Nanoparticles: Everyday Life

  • Nanoparticles are prevalent in everyday life.
  • They can be unintentionally produced, often linked to air pollution.
  • Many are engineered for various applications.

Examples of Exposure

  • Brushing teeth
  • Washing hair
  • Using deodorant
  • Consuming food (cappuccino, yogurt)
  • Environmental exposure during commutes (walking in traffic)
  • Occupational exposure (dental repair clinic)
  • Recreational exposure (sunscreen at the beach)
  • Smoking (cigarette break)

Sources of Nanoparticles

  • Atmospheric aerosols: Dust, sea salt, organic carbon, sulphate.
  • Industrial exhaust fumes.
  • Traffic debris and exhaust.
  • Volcanic eruptions (sulfur dioxide).

Airborne Particle Size Classification

  • Aerosols range in size: from micrometer-sized particles (dust and fine dust) down to nanoparticles (ultrafine dust).

Air Pollution Hotspots

  • Examples were given of cities and their air pollution levels: Dublin, Penang, Bahrain.

Nanoparticles in Tobacco Smoke

  • Surface area: 70-100 m\textsuperscript{2}
  • Deposition: 10^{10} - 10^{12} fine particles deposit in the lung/day
  • Size range: approximately 10 nm to 700 nm, with a peak around 150 nm.

Applications of Inorganic Nanoparticles

  • Nanoparticles have numerous applications across various industries.

Nanoparticles in the Food Chain

  • Nanotechnology is used in the food industry for various purposes.

Titanium Dioxide (TiO\textsuperscript{2}) Concentration in Food

  • Estimate for U.S. population:
    • Children (<10 years): Average intake of 1-2 mg TiO\textsuperscript{2} per kilogram body weight per day.
    • Other consumer age groups: Approximately 0.2-0.7 mg TiO\textsuperscript{2}/kg bw/day.

Uptake, Biodistribution, and Clearance

  • Question: Where do inhaled or ingested nanoparticles end up in the body?

Size-Dependent Deposition in the Lungs

  • The smaller the particulate matter (PM), the deeper it penetrates into the lung.
  • Approximately 1% of inhaled PM remains in the lung.
  • Different regions of the respiratory system: Nasopharyngeal, Tracheobronchial, Alveolar

Clearance Mechanisms of Deposited Particles

  • Two major pathways:
    • Mucociliary escalator (tracheobronchial region).
    • Phagocytosis by macrophages (alveoli).

Escape into Lymphatic System or Circulation

  • Nanoparticles can escape the lungs and enter the lymphatic system or blood circulation.

Nanoparticles Crossing Biological Barriers

  • Translocation depends on the size and surface properties of the particles.
  • Particles < ~34 nm & noncationic (not positively charged) can cross protective barriers like lung epithelium and endothelium of lymphatic or blood vessels.
  • Very small particles (< 6 nm) are relatively quickly cleared by the kidneys and secreted in urine.

Secondary Biodistribution

  • Nanoparticles can cross natural barriers, including the blood-brain barrier.
  • Example: Tobacco smoke reduces monoamine oxidase (MAO) levels by 33%-43%. MAO indirectly affects blood pressure.
  • Absorbed nanoparticles can travel to peripheral organs and affect their functions.

Ingested Nanoparticles

  • Translocation of polystyrene micro/nanospheres across the intestinal wall.
  • A significant fraction of administered particles can cross the intestinal wall.

Cellular Internalization of Micro/Nanoparticles

  • Microscale particles are taken up by phagocytes (macrophages).
  • Small nanoparticles can be taken up by various cell types through endocytosis.
  • Phagocytosis: >750 nm
  • Pinocytosis: ~<2000 nm
  • Endocytosis: ~<100 nm