nanoparticles, once exposed to plasma or clusterin (apolipoprotein J), decreased
non-specific cellular uptake. However, this was again an in vitro study. And the
delicate, but sometimes definitively different, in vivo condition should be investigated for their effect upon non-specific cellular uptake, targeted receptor mediated
uptake to the target cells or uptake by immune cells especially macrophages.
Zwitterion capsulation was also reported using phosphatidylinositol as zwitterion
and capsulation methods using liposome as capsules [55]. Similarly to but unlike
Jeong’s method of using micelle [42], they used liposome (lipid bilayer) to wrap the
gold nanoparticles. They called the final product as the artificial viral nanoparticles
as they mimicked membraned viruses. The effect of corona adsorption was modestly considered for in vitro and subcutaneous injection in vivo experiments.
18.4 Radiolabeling with PEGylation or Zwitterion
Coating of Nanoparticles
There are two methods of PEGylation, one of which is the functionalization of the
surface and then the consequent conjugation of PEGs or small zwitterions at the
later step. The density and shape of the PEGs on the surface of the nanoparticles are
well known factors to influence the physiological behavior of the PEG or
zwitterion-coated nanoparticles. The other method is simultaneous encapsulation
using Jeong’s method. This has become more and more popular because if we
adopt the sequential method, this PEGylation and binding of other ligands and
chelators needed further repeated steps of binding and purification. Simultaneity of
PEGylation and ligand/chelator binding was enabled by micelle encapsulation
which evolved from the first report by Dubertret and optimized by Jeong [42].
Hydrophilization of nanomaterials using the micelle encapsulation method was
first proposed by Dubertret et al. [56]. Via several evolutions of methods [57, 58]
functional biomolecules were introduced successfully [59]. Jeong’s group integrated these proposed methods to devise the simplest method of mixing, vortexing,
and size exclusion chromatography yielding active multi-specific nanoparticles
[42]. By exploiting this one-step method under mild conditions to preserve ligand
integrity, feasibility of multiplexing is now being investigated to embrace both
therapeutic and diagnostic radionuclides simultaneously (Fig. 18.7) [43, 60]. The
key step of manufacturing here is how we make micelles containing mixtures of
linear or branched PEGs, ligands and chelators optimally for the further use in the
next step of capsulation.
There are two approaches, pre- and post-labeling methods, for radiolabeling of
these surface modified nanomaterials (Fig. 18.8) [61]. Pre-labeling method can be
used for the nanomaterials containing the conjugation motifs on the surface and
post-labeling method for the chelators on the surface. Very often, the nanomaterials
340
D. S. Lee and Y.-S. Lee
non-specific cellular uptake. However, this was again an in vitro study. And the
delicate, but sometimes definitively different, in vivo condition should be investigated for their effect upon non-specific cellular uptake, targeted receptor mediated
uptake to the target cells or uptake by immune cells especially macrophages.
Zwitterion capsulation was also reported using phosphatidylinositol as zwitterion
and capsulation methods using liposome as capsules [55]. Similarly to but unlike
Jeong’s method of using micelle [42], they used liposome (lipid bilayer) to wrap the
gold nanoparticles. They called the final product as the artificial viral nanoparticles
as they mimicked membraned viruses. The effect of corona adsorption was modestly considered for in vitro and subcutaneous injection in vivo experiments.
18.4 Radiolabeling with PEGylation or Zwitterion
Coating of Nanoparticles
There are two methods of PEGylation, one of which is the functionalization of the
surface and then the consequent conjugation of PEGs or small zwitterions at the
later step. The density and shape of the PEGs on the surface of the nanoparticles are
well known factors to influence the physiological behavior of the PEG or
zwitterion-coated nanoparticles. The other method is simultaneous encapsulation
using Jeong’s method. This has become more and more popular because if we
adopt the sequential method, this PEGylation and binding of other ligands and
chelators needed further repeated steps of binding and purification. Simultaneity of
PEGylation and ligand/chelator binding was enabled by micelle encapsulation
which evolved from the first report by Dubertret and optimized by Jeong [42].
Hydrophilization of nanomaterials using the micelle encapsulation method was
first proposed by Dubertret et al. [56]. Via several evolutions of methods [57, 58]
functional biomolecules were introduced successfully [59]. Jeong’s group integrated these proposed methods to devise the simplest method of mixing, vortexing,
and size exclusion chromatography yielding active multi-specific nanoparticles
[42]. By exploiting this one-step method under mild conditions to preserve ligand
integrity, feasibility of multiplexing is now being investigated to embrace both
therapeutic and diagnostic radionuclides simultaneously (Fig. 18.7) [43, 60]. The
key step of manufacturing here is how we make micelles containing mixtures of
linear or branched PEGs, ligands and chelators optimally for the further use in the
next step of capsulation.
There are two approaches, pre- and post-labeling methods, for radiolabeling of
these surface modified nanomaterials (Fig. 18.8) [61]. Pre-labeling method can be
used for the nanomaterials containing the conjugation motifs on the surface and
post-labeling method for the chelators on the surface. Very often, the nanomaterials
340
D. S. Lee and Y.-S. Lee