Nanoparticle Cell Penetration - Aerosols: Measurement, Dosimetry, and Health Effects - page 217

9 Nanoparticle Cell Penetration
Steven M. Hankin and Craig A. Poland
CONTENTS
9.1 Introduction .......................................................................................................................... 217
9.2 Particle Interactions with Cells of the Respiratory System .................................................. 217
9.3 Translocation across the Pulmonary Interstitium: The Inluence of Size, Surface Area,
and Aspect Ratio................................................................................................................... 219
9.4 Translocation to the Circulatory System .............................................................................. 220
9.5 Translocation to the Brain .................................................................................................... 221
9.6 Conclusion ............................................................................................................................ 223
Acknowledgment ........................................................................................................................... 223
References...................................................................................................................................... 224
9.1 INTRODUCTION
Following inhalation, nanoparticles must cross cellular barriers to enter the body further. In order
for a substance to enter a cell's interior, it must pass through the diffuse layer surrounding the
cell and the plasma membrane which segregates the internal and external environments of a cell
and regulates the entry and exit of substances into and out of the cell. The uptake of substances
is accomplished via a variety of processes that can be described as active (energy dependent) or
passive (energy independent). There are a number of clearly deined mechanisms for crossing the
plasma membrane that include diffusion, facilitated diffusion, active transport, and endocytosis.
Understanding the speciic processes and physicochemical factors controlling the ability of nanopar-
ticles to cross barriers, in particular epithelial cells, is key to understanding the intracellular fate as
well as the potential for distribution of nanoparticles around the body.
The respiratory system can be divided into upper (nasal cavity, pharynx, and larynx) and lower
(trachea, primary bronchi, and alveoli) sections. The respiratory system is lined with a barrier
of epithelial cells, whose structure and function differ between parts of the pulmonary system.
Epithelial cells form a conluent barrier in healthy tissues and control the movement of substances
in both directions across the epithelium. Damage to the epithelium by toxicants or disease can lead
to an increase in permeability and, therefore, toxicant absorption into the body. Toxicants may also
be taken up directly into the cell and then pass through the epithelial cell into the interstitium or
cardiovascular system. This is known as the transcellular route of absorption (Figure 9.1). The upper
section of the respiratory system presents a potential route of entry to the central nervous system
(CNS) via transport along nerves. In addition, if inhaled nanoparticles cross the lung epithelium and
become bloodborne, they may have the potential to gain access to the blood-brain barrier (BBM).
9.2 PARTICLE INTERACTIONS WITH CELLS OF THE RESPIRATORY SYSTEM
The size of many nanoparticles is similar to biological macromolecules such as proteins and DNA,
as well as biological structures such as bacteria and viruses, all of which are readily taken up by
cells, including lung cells. Vesicular transport exists in lung epithelial cells, since the existence of
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