due to the complexity of the core@shell structure and the reduced stability in vivo
(Fig. 17.2b). By creating a big cavity inside each MSN, and functionalizing the
particle with organic dyes, targeting antibody and radioisotopes, Cai and his group
later developed a hollow MSN (or HMSN) based nanoconjugate, and demonstrated a
significantly enhanced tumor active targeting and drug delivery efficacy (Fig. 17.2c)
[42]. Quantitative PET imaging study showed an over 3-fold higher tumor uptake in
the target area when compared with the non-targeted group, making
64
Cu–NOTA–
HMSN–ZW800–TRC105 one of the few vasculature targeting nanoparticles with
*10%ID/g tumor uptake. With the presence of hollow space inside each HMSN,
doxorubicin-loading capacity was 3–5 times higher when compared with pure MSN.
The liver and spleen uptake was as high as the previously reported MSN counterparts
[40, 43]. Instead of using a traditional chelator-based radiolabeling technique, the
same group also developed a chelator-free method to stably label porous silica
nanoparticles with zirconium-89 (
89 Zr, t 1/2 = 78 h) [44]. Using such technique, the
authors demonstrated the feasibility of creating a self-destructible and biodegradable
mesoporous silica (bMSN) drug carrier which was intrinsically labeled with
89 Zr and
conjugated with antibody for targeting the tumor vasculature (Fig. 17.2d) [45].
Chelator-free
89 Zr labeling demonstrated excellent yield and in vivo stability with
marginal
89 Zr detachment and bone uptake. Careful tailoring of the synthesis of [
89 Zr]
bMSN–PEG–TRC105 also resulted in excellent CD105 specificity, which was confirmed by extensive in vivo and ex vivo testing. Vascular targeting exhibited greater
than threefold enhancement in absolute tumor uptake and normal tissue contrast,
when compared with enhanced permeability and retention (EPR) dependent uptake of
the nanoconjugates. Dominant liver and spleen uptake was observed as well.
Similar PK (relatively short blood circulation half-life, no renal clearance, dominant
liver and spleen uptake, low tumor accumulation rate) was repeatedly found with
MSNs labeled with other radioisotopes, such as radioarsenic [46] and titanium-45
[47]. MSNs were conjugated with different targeting ligands [43, 48], and other
radiolabeled nanoparticles, such as nanographene [49–51], iron oxide nanoparticles
[52, 53], Gd 2 O 2 S:Eu [54, 55], reduced graphene oxide-iron oxide nanoparticles [56],
and many others [57–61]. All these radiolabeled nanoparticles had a greater than
10 nm HD size. In the next section, we will review the size-dependent PK of radiolabeled quantum dots.
17.2.2 Radiolabeled Quantum Dots
Fluorescent semiconductor quantum dots (QDs) have attracted tremendous attention in the field of biomedical imaging over the last 3 decades due to their superior
optical properties over conventional organic dyes [62–69]. As mentioned above,
successful surface protection (i.e., PEGylation) could neutralize the surface negative charge and improve in vivo stability of radiolabeled silica nanoparticles,
leading to a prolonged blood circulation half-life and reduced RES uptake. This was
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F. Chen
(Fig. 17.2b). By creating a big cavity inside each MSN, and functionalizing the
particle with organic dyes, targeting antibody and radioisotopes, Cai and his group
later developed a hollow MSN (or HMSN) based nanoconjugate, and demonstrated a
significantly enhanced tumor active targeting and drug delivery efficacy (Fig. 17.2c)
[42]. Quantitative PET imaging study showed an over 3-fold higher tumor uptake in
the target area when compared with the non-targeted group, making
64
Cu–NOTA–
HMSN–ZW800–TRC105 one of the few vasculature targeting nanoparticles with
*10%ID/g tumor uptake. With the presence of hollow space inside each HMSN,
doxorubicin-loading capacity was 3–5 times higher when compared with pure MSN.
The liver and spleen uptake was as high as the previously reported MSN counterparts
[40, 43]. Instead of using a traditional chelator-based radiolabeling technique, the
same group also developed a chelator-free method to stably label porous silica
nanoparticles with zirconium-89 (
89 Zr, t 1/2 = 78 h) [44]. Using such technique, the
authors demonstrated the feasibility of creating a self-destructible and biodegradable
mesoporous silica (bMSN) drug carrier which was intrinsically labeled with
89 Zr and
conjugated with antibody for targeting the tumor vasculature (Fig. 17.2d) [45].
Chelator-free
89 Zr labeling demonstrated excellent yield and in vivo stability with
marginal
89 Zr detachment and bone uptake. Careful tailoring of the synthesis of [
89 Zr]
bMSN–PEG–TRC105 also resulted in excellent CD105 specificity, which was confirmed by extensive in vivo and ex vivo testing. Vascular targeting exhibited greater
than threefold enhancement in absolute tumor uptake and normal tissue contrast,
when compared with enhanced permeability and retention (EPR) dependent uptake of
the nanoconjugates. Dominant liver and spleen uptake was observed as well.
Similar PK (relatively short blood circulation half-life, no renal clearance, dominant
liver and spleen uptake, low tumor accumulation rate) was repeatedly found with
MSNs labeled with other radioisotopes, such as radioarsenic [46] and titanium-45
[47]. MSNs were conjugated with different targeting ligands [43, 48], and other
radiolabeled nanoparticles, such as nanographene [49–51], iron oxide nanoparticles
[52, 53], Gd 2 O 2 S:Eu [54, 55], reduced graphene oxide-iron oxide nanoparticles [56],
and many others [57–61]. All these radiolabeled nanoparticles had a greater than
10 nm HD size. In the next section, we will review the size-dependent PK of radiolabeled quantum dots.
17.2.2 Radiolabeled Quantum Dots
Fluorescent semiconductor quantum dots (QDs) have attracted tremendous attention in the field of biomedical imaging over the last 3 decades due to their superior
optical properties over conventional organic dyes [62–69]. As mentioned above,
successful surface protection (i.e., PEGylation) could neutralize the surface negative charge and improve in vivo stability of radiolabeled silica nanoparticles,
leading to a prolonged blood circulation half-life and reduced RES uptake. This was
318
F. Chen