multifunctional nanoparticles [12]. This method has been successfully applied other
hard core nanomaterials, such as iron oxide particles with a diameter of 5 nm [13,
14], upconverting NPs (UCNPs) with a diameter of 35 nm [15]. After the micelle
encapsulation, total size of nanoparticle is increased for 5–6 nm, and this increase is
matched with the length of PEGs from Tween 60
® . The size distribution of
encapsulated nanoparticles is quite narrow (poly dispersity index: PDI < 0.2) by
dynamic light scattering (DLS) measurement [13, 14]. Because the size of nanomaterials affect the in vivo distribution of nanomaterials, nanomaterials should
maintain the narrow size distribution after core synthesis and any chemical modification including hydrophilization and radiolabeling.
For construction of clickable radionanomedicine platform, we can simply mix
the alkyl-chained click moiety, such as azide- or diarylcyclooctyne (DBCO)-C 18 ,
with Tween 60
® (Fig. 12.1). This nano-platform can be used for further modification for target molecule ligation, therapeutic drug conjugation or radio/
fluorescent-labeling.
12.3 Conjugation of Targeting Molecules
Enhanced permeability and retention (EPR) effect has been believed to constitute a
major mechanism for the passive delivery and accumulation of nanomaterials in the
tumor tissue for several decades [16]. Despite the success of nanomedicines without
targeting molecules, in early approval from US Food and Drug Administration
(FDA), such as Doxil
® , doxorubicin containing liposomal system, or Abraxane
® ,
paclitaxel-albumin nanoparticles, which suggested EPR was sufficient for drug
efficacy, this EPR effect is still under controversy because of its poor treatment
score in clinical setting probably due to the heterogeneity of tumor and microenvironment [17, 18]. To overcome this problem, active or disease-specific targeting
strategy would be another option for nanomedicines, which can be accomplished by
attaching targeting molecules on the surface of nanomaterials. Considering that the
click chemistry has the great advantage over conventional conjugation method,
there are so far the limited numbers of application of this click chemistry on
nanomaterials. Therefore, here we summarize all the possible targeting molecules
that the investigators can use click chemistry for modification but not. However, all
these targeting molecules, which were well summarized in Theranostics [19], as
will be discussed below can be modified with click chemical and applied for click
chemistry.
12.3.1 Small Molecules
There are huge varieties of target disease and disease-specific targeting molecules,
and these molecules are categorized by size from small molecules to
234
Y.-S. Lee et al.
hard core nanomaterials, such as iron oxide particles with a diameter of 5 nm [13,
14], upconverting NPs (UCNPs) with a diameter of 35 nm [15]. After the micelle
encapsulation, total size of nanoparticle is increased for 5–6 nm, and this increase is
matched with the length of PEGs from Tween 60
® . The size distribution of
encapsulated nanoparticles is quite narrow (poly dispersity index: PDI < 0.2) by
dynamic light scattering (DLS) measurement [13, 14]. Because the size of nanomaterials affect the in vivo distribution of nanomaterials, nanomaterials should
maintain the narrow size distribution after core synthesis and any chemical modification including hydrophilization and radiolabeling.
For construction of clickable radionanomedicine platform, we can simply mix
the alkyl-chained click moiety, such as azide- or diarylcyclooctyne (DBCO)-C 18 ,
with Tween 60
® (Fig. 12.1). This nano-platform can be used for further modification for target molecule ligation, therapeutic drug conjugation or radio/
fluorescent-labeling.
12.3 Conjugation of Targeting Molecules
Enhanced permeability and retention (EPR) effect has been believed to constitute a
major mechanism for the passive delivery and accumulation of nanomaterials in the
tumor tissue for several decades [16]. Despite the success of nanomedicines without
targeting molecules, in early approval from US Food and Drug Administration
(FDA), such as Doxil
® , doxorubicin containing liposomal system, or Abraxane
® ,
paclitaxel-albumin nanoparticles, which suggested EPR was sufficient for drug
efficacy, this EPR effect is still under controversy because of its poor treatment
score in clinical setting probably due to the heterogeneity of tumor and microenvironment [17, 18]. To overcome this problem, active or disease-specific targeting
strategy would be another option for nanomedicines, which can be accomplished by
attaching targeting molecules on the surface of nanomaterials. Considering that the
click chemistry has the great advantage over conventional conjugation method,
there are so far the limited numbers of application of this click chemistry on
nanomaterials. Therefore, here we summarize all the possible targeting molecules
that the investigators can use click chemistry for modification but not. However, all
these targeting molecules, which were well summarized in Theranostics [19], as
will be discussed below can be modified with click chemical and applied for click
chemistry.
12.3.1 Small Molecules
There are huge varieties of target disease and disease-specific targeting molecules,
and these molecules are categorized by size from small molecules to
234
Y.-S. Lee et al.