(core-shell structure). More specifically for radionanomaterials, surface modification can stabilize the radioisotope cargo(s) loaded on the given nanomaterial [9].
Surface coating can also determine how radionanomaterials interact with biological environments [10]. After administration in vivo, radionanomaterials usually
face the interaction and adsorption of encountered molecules, including ions, lipids,
saccharides, and particularly proteins [11], all of which can form ‘corona’ on the
surface of radionanomaterials [12]. This ‘re-coating’ of radionanomaterials is
mediated by electrostatic interactions, hydrogen bonding, hydrophobic interactions,
or Van der Waals force [13]. Thus, proper surface engineering of radionanomaterials can be crucial to tune the interactions (e.g. reduce undesired ones) between
them and those biological molecules. For instance, by adjusting the surface properties (e.g. charges), radionanomaterials can have higher escape rate from phagocyte system, lower adsorption onto plasma proteins, or more specific accumulation
into given cell populations [14]. Additionally, surface coating agents such as PEG
can be very useful to regulate the residence time of radionanomaterials in vivo [10,
15]. Thus, surface properties of radionanomaterials contribute directly to their
in vivo toxicity [16].
Various biomolecules, e.g. peptides, antibodies, proteins etc., can be attached to
the surface of radionanomaterials relying on the proper surface modification [17,
18]. The incorporation of these molecules (termed “targeting ligands”) can facilitate
the trafficking of radionanomaterials more efficiently into the target tissue. Despite
the fact that nanomaterials can possess the well-known enhanced permeability and
retention (EPR) effect and accumulate in tissues with disrupted/irregular vasculature
structures (e.g. passive targeting in tumor) [19], tissue permeability can vary significantly even within the same individual. Thus, these biomolecules enable
radionanomaterials to undergo ligand-directed cell targeting and tissue microenvironment targeting. An important consideration during the targeting ligand conjunction is that the targeting moieties should be avoided to bury in the protein
‘corona’ when administered in vivo. Also, the ligand molecule numbers on nanomaterial surface should be carefully investigated since previous studies have
revealed that high-density surface ligands can accelerate the clearance of nanomaterials and compromise their targeting efficiency [20]. Thus, optimizing the
ligand number on radionanomaterials does not indicate just increasing the ligand
number per nanomaterial. On the other hand, biomolecules like cell-penetrating
peptides (CPPs) can enhance the general cell permeability of nanomaterials [21].
CPPs can facilitate nanoparticle internalization to various types of cells and are
especially useful to deliver nanomaterials otherwise impermeable for given cell
types [22].
Surface modification is sometimes important to bring radioisotopes into nanomaterials. In those scenarios, radioisotopes were actually incorporated into the
surface coating molecules (or extra surface modification layer) [23]. This strategy is
particularly suitable when the isotopes loaded on nanomaterials have a relatively
short physical half-life (e.g.
18
F (118 min),
99m Tc (6 h), etc.). One obvious limitation of this method is that the stability of surface coating becomes the limiting
factor for the overall efficacy of radionanomedicines. However, compared with
10 Surface Modification of Radionanomedicine
187
Surface coating can also determine how radionanomaterials interact with biological environments [10]. After administration in vivo, radionanomaterials usually
face the interaction and adsorption of encountered molecules, including ions, lipids,
saccharides, and particularly proteins [11], all of which can form ‘corona’ on the
surface of radionanomaterials [12]. This ‘re-coating’ of radionanomaterials is
mediated by electrostatic interactions, hydrogen bonding, hydrophobic interactions,
or Van der Waals force [13]. Thus, proper surface engineering of radionanomaterials can be crucial to tune the interactions (e.g. reduce undesired ones) between
them and those biological molecules. For instance, by adjusting the surface properties (e.g. charges), radionanomaterials can have higher escape rate from phagocyte system, lower adsorption onto plasma proteins, or more specific accumulation
into given cell populations [14]. Additionally, surface coating agents such as PEG
can be very useful to regulate the residence time of radionanomaterials in vivo [10,
15]. Thus, surface properties of radionanomaterials contribute directly to their
in vivo toxicity [16].
Various biomolecules, e.g. peptides, antibodies, proteins etc., can be attached to
the surface of radionanomaterials relying on the proper surface modification [17,
18]. The incorporation of these molecules (termed “targeting ligands”) can facilitate
the trafficking of radionanomaterials more efficiently into the target tissue. Despite
the fact that nanomaterials can possess the well-known enhanced permeability and
retention (EPR) effect and accumulate in tissues with disrupted/irregular vasculature
structures (e.g. passive targeting in tumor) [19], tissue permeability can vary significantly even within the same individual. Thus, these biomolecules enable
radionanomaterials to undergo ligand-directed cell targeting and tissue microenvironment targeting. An important consideration during the targeting ligand conjunction is that the targeting moieties should be avoided to bury in the protein
‘corona’ when administered in vivo. Also, the ligand molecule numbers on nanomaterial surface should be carefully investigated since previous studies have
revealed that high-density surface ligands can accelerate the clearance of nanomaterials and compromise their targeting efficiency [20]. Thus, optimizing the
ligand number on radionanomaterials does not indicate just increasing the ligand
number per nanomaterial. On the other hand, biomolecules like cell-penetrating
peptides (CPPs) can enhance the general cell permeability of nanomaterials [21].
CPPs can facilitate nanoparticle internalization to various types of cells and are
especially useful to deliver nanomaterials otherwise impermeable for given cell
types [22].
Surface modification is sometimes important to bring radioisotopes into nanomaterials. In those scenarios, radioisotopes were actually incorporated into the
surface coating molecules (or extra surface modification layer) [23]. This strategy is
particularly suitable when the isotopes loaded on nanomaterials have a relatively
short physical half-life (e.g.
18
F (118 min),
99m Tc (6 h), etc.). One obvious limitation of this method is that the stability of surface coating becomes the limiting
factor for the overall efficacy of radionanomedicines. However, compared with
10 Surface Modification of Radionanomedicine
187