a part of the protein corona formation process. However, not all the circulating
proteins can facilitate phagocytosis of the NPs.
The efficiency of opsonization can differ according to their surface properties
including charge and hydrophobicity. The characteristics and consequences of the
protein corona formation have been well described in several review articles and
another chapter “Corona and its Consequences”. This protein adsorption significantly affect the biodistribution of the NPs, speedy recognition and clearance by
MPS (also called the reticuloendothelial system; RES) in particular [28]. The
hydrophobic and electrostatic interactions are the main forces for protein adsorption
on NPs [29, 30]. Higher charge and higher hydrophobicity of NPs are the major
factors to make NPs prone to be opsonized [31, 32]. Without the opsonization,
phagocytes are generally not able to capture the foreign materials. After
opsonization, bound opsonins such as complement may undergo a conformational
change to have an activated protein structure that can be well recognized by the
receptors of the phagocytes [33].
19.3.2 Interaction Between MPS and Nanoparticles
Circulating nanomaterials are recognized after opsonization by tissue macrophage
system, MPS also known as RES [34]. MPS is a part of the innate immune system
which can be found in kidneys, lungs, bone marrow, liver, spleen and lymph nodes
etc. MPS eliminates foreign invaders non-specifically via direct interactions with
the phagocytic cells. Kupffer cells in the liver sinusoid are a major portion of MPS
which makes up 80–90% total body macrophage population. Further detailed
information regarding innate immune response to NPs is found in the chapter
“Innate Immunity”. NPs cleared by MPS are not excreted from body system
shortly, because NPs are not well dissolved by a chemical reaction in lysosomes of
the phagocytes (Fig. 19.6) [35–38]. This can be problematic since persistence in the
phagocytic system can induce cell/tissue toxicity [39, 40]. Also, fast clearance to
MPS results in a short blood circulation time. Short blood circulation time effectively limits the targeting efficiency of the NPs, especially when NPs are targeted by
passive targeting. Lower or slower MPS clearance of NPs is challenging in most
cases but mandatory for effective targeted imaging/therapy using NPs. Thus, MPS
recognition of NPs is the major hurdle for development and clinical translation of
the targeted delivery of NPs [28, 34, 41, 42].
Lowering MPS recognition of the NPs, i.e. the stealth effect of NPs, can be
primarily achieved by reducing the opsonization and there are several strategies
(Fig. 19.7). Polysaccharides (dextrans) and polyethylene glycols (PEGs) are the
two popular methods to reduce opsonization [43]. Flexibility and high
hydrophilicity of these polymers interfere the hydrophobic interaction between NPs
and blood proteins. However, when the same PEGylated NPs are injected into the
same animal second time, MPS recognition of the NPs become faster resulting in
faster blood clearance. This phenomenon is known as Accelerated Blood Clearance
356
H.-J. Im
proteins can facilitate phagocytosis of the NPs.
The efficiency of opsonization can differ according to their surface properties
including charge and hydrophobicity. The characteristics and consequences of the
protein corona formation have been well described in several review articles and
another chapter “Corona and its Consequences”. This protein adsorption significantly affect the biodistribution of the NPs, speedy recognition and clearance by
MPS (also called the reticuloendothelial system; RES) in particular [28]. The
hydrophobic and electrostatic interactions are the main forces for protein adsorption
on NPs [29, 30]. Higher charge and higher hydrophobicity of NPs are the major
factors to make NPs prone to be opsonized [31, 32]. Without the opsonization,
phagocytes are generally not able to capture the foreign materials. After
opsonization, bound opsonins such as complement may undergo a conformational
change to have an activated protein structure that can be well recognized by the
receptors of the phagocytes [33].
19.3.2 Interaction Between MPS and Nanoparticles
Circulating nanomaterials are recognized after opsonization by tissue macrophage
system, MPS also known as RES [34]. MPS is a part of the innate immune system
which can be found in kidneys, lungs, bone marrow, liver, spleen and lymph nodes
etc. MPS eliminates foreign invaders non-specifically via direct interactions with
the phagocytic cells. Kupffer cells in the liver sinusoid are a major portion of MPS
which makes up 80–90% total body macrophage population. Further detailed
information regarding innate immune response to NPs is found in the chapter
“Innate Immunity”. NPs cleared by MPS are not excreted from body system
shortly, because NPs are not well dissolved by a chemical reaction in lysosomes of
the phagocytes (Fig. 19.6) [35–38]. This can be problematic since persistence in the
phagocytic system can induce cell/tissue toxicity [39, 40]. Also, fast clearance to
MPS results in a short blood circulation time. Short blood circulation time effectively limits the targeting efficiency of the NPs, especially when NPs are targeted by
passive targeting. Lower or slower MPS clearance of NPs is challenging in most
cases but mandatory for effective targeted imaging/therapy using NPs. Thus, MPS
recognition of NPs is the major hurdle for development and clinical translation of
the targeted delivery of NPs [28, 34, 41, 42].
Lowering MPS recognition of the NPs, i.e. the stealth effect of NPs, can be
primarily achieved by reducing the opsonization and there are several strategies
(Fig. 19.7). Polysaccharides (dextrans) and polyethylene glycols (PEGs) are the
two popular methods to reduce opsonization [43]. Flexibility and high
hydrophilicity of these polymers interfere the hydrophobic interaction between NPs
and blood proteins. However, when the same PEGylated NPs are injected into the
same animal second time, MPS recognition of the NPs become faster resulting in
faster blood clearance. This phenomenon is known as Accelerated Blood Clearance
356
H.-J. Im