and biocompatibility of QDs has been reported by Choi et al. [113]. Development
of biocompatible QDs together with a reduction in QD toxicity can thus accelerate
the use of these NPs in tumor imaging improve the possibility of clinical translation.
2.5 Silica Nanoparticles
Since the first report of the use of silica in biological applications [114], silica
particles have attracted increasing interest due to their remarkable potential as
nanoplatforms for imaging, therapy or both. In fact, Therasphere
® , a system
composed of silica microspheres associated with Yttrium-90 has been successfully
used in the clinic as a therapeutic agent for hepatocellular carcinoma and colon
metastasis derived from hepatic cancer [115–117]. More recently, dye-doped
ultrasmall silica NPs (SiNPs), called Cornell dots (or C-dots), were approved by the
United States Food and Drug Administration (FDA) as an investigational new drug
(IND) and have entered clinical investigation in melanoma patients [118]. The
C-dots, of around 7 nm in size contain the Cy5 dye enclosed in its interior and the
cyclic cRGDY peptide ligands, as well as the isotope
124 I attached to its surface.
This type of SiNP has shown excellent biological properties such as specific
accumulation in tumor tissues with high affinity and avidity in a v b 3
integrin-expressing melanomas and the capacity of being renal clearable with relatively high efficiency [118]. In a micro-dosing clinical trial, these Cy5 dye-loaded
C dots were labeled with
124
I for PET/CT imaging of integrin-expressing lesions.
The tracers were well tolerated, exhibited good in vivo stability, reproducible
pharmacokinetic signatures consistent with renal clearance, and preferential accumulation at the target site [119].
Unlike many other nanomaterials, SiNPs do not possess a novel property, except
for the increase in surface area that is natural to every nanomaterial. SiNPs also do
not have any special optical or magnetic properties, such as light absorption or
magnetic field interference. However, SiNPs present a major advantage of having
very well-defined and easily tunable properties such as crystallinity, size, morphology, and porosity [120]. In addition, chemical groups on the surface of SiNPs
allow various well-established functionalization steps granting precise control of
drug or chemical loading, PEGylation, conjugation with active targets and, consequently, the modulation of in vivo behavior [121]. Other features including easy
and inexpensive synthesis, water dispersibility, high stability and biocompatibility,
scalable synthetic availability, large pore volume for efficient and enhanced
immobilization/encapsulation of drug molecules or biomolecules makes silica NPs
particularly suitable for a diverse range of biological applications [122]. Also, silica
is “generally recognized as safe” (ID Code: 14808–60–7) for oral administration by
the FDA since 2010, which improves the chances of clinical translation of any SiNP
formulation [123].
There are two major types of SiNPs: solid SiNPs (SSiNPs), and mesoporous
silica NPs (MSNs) with interior channels and an exterior particle surface, which can
2 Exogenous Radionanomedicine: Inorganic Nanomaterials
27
of biocompatible QDs together with a reduction in QD toxicity can thus accelerate
the use of these NPs in tumor imaging improve the possibility of clinical translation.
2.5 Silica Nanoparticles
Since the first report of the use of silica in biological applications [114], silica
particles have attracted increasing interest due to their remarkable potential as
nanoplatforms for imaging, therapy or both. In fact, Therasphere
® , a system
composed of silica microspheres associated with Yttrium-90 has been successfully
used in the clinic as a therapeutic agent for hepatocellular carcinoma and colon
metastasis derived from hepatic cancer [115–117]. More recently, dye-doped
ultrasmall silica NPs (SiNPs), called Cornell dots (or C-dots), were approved by the
United States Food and Drug Administration (FDA) as an investigational new drug
(IND) and have entered clinical investigation in melanoma patients [118]. The
C-dots, of around 7 nm in size contain the Cy5 dye enclosed in its interior and the
cyclic cRGDY peptide ligands, as well as the isotope
124 I attached to its surface.
This type of SiNP has shown excellent biological properties such as specific
accumulation in tumor tissues with high affinity and avidity in a v b 3
integrin-expressing melanomas and the capacity of being renal clearable with relatively high efficiency [118]. In a micro-dosing clinical trial, these Cy5 dye-loaded
C dots were labeled with
124
I for PET/CT imaging of integrin-expressing lesions.
The tracers were well tolerated, exhibited good in vivo stability, reproducible
pharmacokinetic signatures consistent with renal clearance, and preferential accumulation at the target site [119].
Unlike many other nanomaterials, SiNPs do not possess a novel property, except
for the increase in surface area that is natural to every nanomaterial. SiNPs also do
not have any special optical or magnetic properties, such as light absorption or
magnetic field interference. However, SiNPs present a major advantage of having
very well-defined and easily tunable properties such as crystallinity, size, morphology, and porosity [120]. In addition, chemical groups on the surface of SiNPs
allow various well-established functionalization steps granting precise control of
drug or chemical loading, PEGylation, conjugation with active targets and, consequently, the modulation of in vivo behavior [121]. Other features including easy
and inexpensive synthesis, water dispersibility, high stability and biocompatibility,
scalable synthetic availability, large pore volume for efficient and enhanced
immobilization/encapsulation of drug molecules or biomolecules makes silica NPs
particularly suitable for a diverse range of biological applications [122]. Also, silica
is “generally recognized as safe” (ID Code: 14808–60–7) for oral administration by
the FDA since 2010, which improves the chances of clinical translation of any SiNP
formulation [123].
There are two major types of SiNPs: solid SiNPs (SSiNPs), and mesoporous
silica NPs (MSNs) with interior channels and an exterior particle surface, which can
2 Exogenous Radionanomedicine: Inorganic Nanomaterials
27