nanomaterials. Thus PEGylation or the surface modification with the same goal of
hydrophilization and stealth effect shall be understood for their efficacy or mechanism regarding whether to achieve this goal.
Corona proteins consist of hard and soft ones, the difference of which lay only in
the binding affinity determining the kinetic fate in the blood or the plasma [14, 15].
Many reports showed that corona-modified nanomaterials act rather differently from
the bare nanomaterials [15–17, 19]. This difference ranged from interaction with
innate immune cells [16], the binding to the target cells [17, 22–25], circulation
time [24–28], endocytosis into the cells [29–31] and final fate of the nanomaterials
inside the cells [19, 22, 26, 27, 31, 32]. This would seem obvious in vivo [23, 24],
however, such was also the case in the investigation done in vitro upon cultured
cells [16, 17, 23, 28, 29, 31]. Serum or plasma-incubated nanomaterials began to be
included in the investigation to simulate the status of systemically-injected nanomaterials in vitro. Consequences of PEGylated nanomaterials are now understood
considering these factors.
Stealth effect was once proposed that PEGylated materials are not recognized by
mononuclear phagocytic system (MPS) and thus increase circulation time almost
indefinitely and have advantageous freedom to find and reach targets. Even passive
targeting strategy was proposed to be enough to deliver sufficient amount of
PEGylated peptides/macromolecules or PEGylated nanomaterials. Stealth effect is
being also recapitulated by further experiments with or without corona wrapping of
the PEGylation of the nanomaterials [27, 28, 33]. As the terminal residues of PEGs
can influence binding of corona proteins and their consequential effect upon the
assumed stealth effect should now be investigated. Different forms of PEGs [11, 12]
and the density of the PEGs over the surface [5–7, 32], in combination with surface
zeta potential as well as the size and even the core contents [5, 6] increase hugely
the combination of the constitution of surface-modified PEGylated ligand-attached
nanomaterials finally decorated with hard/soft corona [23, 25, 30]. PEGylation
might be changed by PPE (polyphosphoester)-coating [28, 34] or zwitterion coating
[35, 36]. The same understanding regarding the biodistribution, targeting and
immune response should be elucidated for these improved coatings just like
PEGylation. Host immune response to certain PEGs were reported and was associated with shortened blood clearance time [37, 38]. Inherent antiPEG antibodies
were reported and speculated to be due to prior unrecognized exposure to PEGs
administered to the skin as cosmetics or to the gastrointestinal tracts as food
additives [39, 40]. PEGylated treatment regimens (Table 18.1) might be also the
source of immunization. PEGylated radioisotope-labeled nanomaterials will meet
the same challenge to achieve the optimal biodistribution and target disposal and
least immune responses. Diagnostic PEGylated radionanomaterials was reported to
reveal easily the improved pharmacokinetic [41] but therapeutic and theranostic
radionanomaterials are meticulously produced considering all the know-hows
acquired when the previous investigators overcame the unpredictability or combining PEGs and peptides/antibodies for successful clinical translation. Finding out
the best PEGylated nanomaterials fit for in vivo theranostic use is a really big
problem desired to be solved.
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D. S. Lee and Y.-S. Lee
hydrophilization and stealth effect shall be understood for their efficacy or mechanism regarding whether to achieve this goal.
Corona proteins consist of hard and soft ones, the difference of which lay only in
the binding affinity determining the kinetic fate in the blood or the plasma [14, 15].
Many reports showed that corona-modified nanomaterials act rather differently from
the bare nanomaterials [15–17, 19]. This difference ranged from interaction with
innate immune cells [16], the binding to the target cells [17, 22–25], circulation
time [24–28], endocytosis into the cells [29–31] and final fate of the nanomaterials
inside the cells [19, 22, 26, 27, 31, 32]. This would seem obvious in vivo [23, 24],
however, such was also the case in the investigation done in vitro upon cultured
cells [16, 17, 23, 28, 29, 31]. Serum or plasma-incubated nanomaterials began to be
included in the investigation to simulate the status of systemically-injected nanomaterials in vitro. Consequences of PEGylated nanomaterials are now understood
considering these factors.
Stealth effect was once proposed that PEGylated materials are not recognized by
mononuclear phagocytic system (MPS) and thus increase circulation time almost
indefinitely and have advantageous freedom to find and reach targets. Even passive
targeting strategy was proposed to be enough to deliver sufficient amount of
PEGylated peptides/macromolecules or PEGylated nanomaterials. Stealth effect is
being also recapitulated by further experiments with or without corona wrapping of
the PEGylation of the nanomaterials [27, 28, 33]. As the terminal residues of PEGs
can influence binding of corona proteins and their consequential effect upon the
assumed stealth effect should now be investigated. Different forms of PEGs [11, 12]
and the density of the PEGs over the surface [5–7, 32], in combination with surface
zeta potential as well as the size and even the core contents [5, 6] increase hugely
the combination of the constitution of surface-modified PEGylated ligand-attached
nanomaterials finally decorated with hard/soft corona [23, 25, 30]. PEGylation
might be changed by PPE (polyphosphoester)-coating [28, 34] or zwitterion coating
[35, 36]. The same understanding regarding the biodistribution, targeting and
immune response should be elucidated for these improved coatings just like
PEGylation. Host immune response to certain PEGs were reported and was associated with shortened blood clearance time [37, 38]. Inherent antiPEG antibodies
were reported and speculated to be due to prior unrecognized exposure to PEGs
administered to the skin as cosmetics or to the gastrointestinal tracts as food
additives [39, 40]. PEGylated treatment regimens (Table 18.1) might be also the
source of immunization. PEGylated radioisotope-labeled nanomaterials will meet
the same challenge to achieve the optimal biodistribution and target disposal and
least immune responses. Diagnostic PEGylated radionanomaterials was reported to
reveal easily the improved pharmacokinetic [41] but therapeutic and theranostic
radionanomaterials are meticulously produced considering all the know-hows
acquired when the previous investigators overcame the unpredictability or combining PEGs and peptides/antibodies for successful clinical translation. Finding out
the best PEGylated nanomaterials fit for in vivo theranostic use is a really big
problem desired to be solved.
336
D. S. Lee and Y.-S. Lee