endothelial and epithelial cells and even hepatocytes as well as professional
phagocytic cells. The difference between immunoglobulins and immunoglobulinbound nanomaterials lies possibly in their presentation pattern. Immune complex
are formed with immunoglobulins against therapeutic antibodies and presented to
tissue-resident macrophages including Kupffer cells, while immunoglobulins on the
nanomaterials’ surface may be hidden and thus may not be detected by anti-Ig
immunoglobulins or anti-Ig TCR.
21.4.3 Macrophages Respond to the Exogenous
Nanomaterials in Spleen
Spleen is the organ in charge of adaptive immunity and innate immunity [45]. Red
pulp sinusoidal macrophages (RpMU) may be tissue-resident macrophages specialized in aged or damaged erythrocyte disposal. However, during infection, circulating monocyte-derived macrophages join the pool of RpMU [56]. Marginal
zone macrophages (MZMU) phagocytize blood-borne pathogens and clear them
from the circulation. Marginal metalophillic macrophages (MMMU) also phagocytize and process the pathogens to present them, in collaboration with DCs, to the
T lymphocyte. MZMUs work for innate immunity and MMMU for adaptive
immunity [56].
PEGylated nanomaterials, if they are administered via intravenous routes, will
arrive at spleen crossing white pulp to reach marginal zones and red pulp. They will
meet either MZMUs or MMMUs (Fig. 21.3). If they mimic LPS and meet TLR4, or
have glycosylphosphatidylinositol (GPI) and meet TLR2/TLR4 or have CpG motif
and meet TLR9, they will be endocytosed by MZMUs as final destiny or by
MMMUs to be presented to immune cells [56]. Extracellular matrix protein,
fibronectin or intracellular DNA binding protein or oxidized low-density lipoprotein
(LDL) were found to be taken up by these splenic macrophages and thus,
surface-mimicry of nanomaterials will make these nanomaterials be treated like
invading pathogens. The possibility of PEGylated nanomaterials to stimulate innate
or adaptive immunity reside in their similarity in structure to invading pathogens.
21.4.4 Prediction of Immune Responses
of Therapeutic-Radioisotope-Labeled Nanomaterials
Therapeutic radioisotopes such as lutetium-177 (
177 Lu) or yttrium-90 (
90
Y) were
shown to be labeled easily with chelators surface-bound to the nanomaterials. In
recent reports, Jeong and others [57] presented their approach of simply modifying
the surface of alkylated nanomaterials simultaneously with PEG, chelator-alkyl
linker, ligand-alkyl linkers or antibodies. This was called encapsulation and the
21 Innate Immunity to Nanomaterials
401
phagocytic cells. The difference between immunoglobulins and immunoglobulinbound nanomaterials lies possibly in their presentation pattern. Immune complex
are formed with immunoglobulins against therapeutic antibodies and presented to
tissue-resident macrophages including Kupffer cells, while immunoglobulins on the
nanomaterials’ surface may be hidden and thus may not be detected by anti-Ig
immunoglobulins or anti-Ig TCR.
21.4.3 Macrophages Respond to the Exogenous
Nanomaterials in Spleen
Spleen is the organ in charge of adaptive immunity and innate immunity [45]. Red
pulp sinusoidal macrophages (RpMU) may be tissue-resident macrophages specialized in aged or damaged erythrocyte disposal. However, during infection, circulating monocyte-derived macrophages join the pool of RpMU [56]. Marginal
zone macrophages (MZMU) phagocytize blood-borne pathogens and clear them
from the circulation. Marginal metalophillic macrophages (MMMU) also phagocytize and process the pathogens to present them, in collaboration with DCs, to the
T lymphocyte. MZMUs work for innate immunity and MMMU for adaptive
immunity [56].
PEGylated nanomaterials, if they are administered via intravenous routes, will
arrive at spleen crossing white pulp to reach marginal zones and red pulp. They will
meet either MZMUs or MMMUs (Fig. 21.3). If they mimic LPS and meet TLR4, or
have glycosylphosphatidylinositol (GPI) and meet TLR2/TLR4 or have CpG motif
and meet TLR9, they will be endocytosed by MZMUs as final destiny or by
MMMUs to be presented to immune cells [56]. Extracellular matrix protein,
fibronectin or intracellular DNA binding protein or oxidized low-density lipoprotein
(LDL) were found to be taken up by these splenic macrophages and thus,
surface-mimicry of nanomaterials will make these nanomaterials be treated like
invading pathogens. The possibility of PEGylated nanomaterials to stimulate innate
or adaptive immunity reside in their similarity in structure to invading pathogens.
21.4.4 Prediction of Immune Responses
of Therapeutic-Radioisotope-Labeled Nanomaterials
Therapeutic radioisotopes such as lutetium-177 (
177 Lu) or yttrium-90 (
90
Y) were
shown to be labeled easily with chelators surface-bound to the nanomaterials. In
recent reports, Jeong and others [57] presented their approach of simply modifying
the surface of alkylated nanomaterials simultaneously with PEG, chelator-alkyl
linker, ligand-alkyl linkers or antibodies. This was called encapsulation and the
21 Innate Immunity to Nanomaterials
401