2.6.2 Upconversion Nanoparticles
Upconversion NPs (UCNPs) are a relatively new class of nanomaterials that have
been studied for biological applications. UCNPs have numerous features that make
them well-suited for therapeutic and diagnostic applications. First, their unprecedented frequency conversion capability is commonly absent in traditional fluorophores [146]. During the upconversion process, the trivalent lanthanide ions, when
embedded in a proper inorganic host lattice, sequentially absorb multiple photons in
order to produce higher energy anti-Stokes luminescence [147]. In a simpler
manner, when UCNPs are excited by a NIR source (e.g., 980 nm), they emit
higher-energy photons in the ultraviolet (UV) to NIR range. Furthermore, they
present other several advantages such as negligible autofluorescence background,
high resistance to photo-bleaching, deeper tissue penetration and less light scattering [148]. The basic structure of UCNPs consists of an inorganic host matrix
(fluorides, oxides, heavy halides etc.), a sensitizer (to enhance UCL efficiency;
Yb
3+ ) and an emitter (Er
3+ , Tm
3+ and Ho
3+ dopant ions). Doping is a commonly
used method to incorporate different functional lanthanide (Ln) ions in the NPs to
achieve multifunctional properties. UCNPs doped with Gd is an example of a tracer
agent that has been used both for MRI and optical imaging [149]. Moreover,
another theranostic application of UCNPs relies on the combination of photoluminescence (PL) imaging with other imaging modalities besides MRI, such as
computed tomography (CT) [150], SPECT [151] and PET [152]. Although only a
few studies have been reported so far, UCNPs have been radiolabeled with
68 Ga
[153],
64 Cu [154] and
124 I [155] through a chelator-based method and with
153 Sm
[156] and
18 F [157] through a chelator-free radiolabeling strategy. In an interesting
study, Rieffel et al. [158], demonstrated the ability of UCNPs as multiplexing
imaging agents, in which a hexamodal porphyrin-phospholipid-coated UCNP
(PoP-UCNP) system was developed. A simple incubation post-labeling method was
carried out by making use of the high affinity of copper for porphyrins resulting in
>80% labeling yield.
64
Cu radiolabeled PEGylated PoP-UCNPs could then be used
for fluorescence, NIR-to-NIR UCL, PET, CT, Cerenkov luminescence, and photoacoustic tomography (PAT) for in vivo lymphatic mapping (Fig. 2.7b).
Altogether, these studies show the vastly improved imaging potential of simple yet
higher-order upconversion NPs for multimodality imaging [158].
2.6.3 Copper Sulfide Nanoparticles
With different types of inorganic nanomaterials available, copper sulfide (CuS) NPs
have become an appealing choice because of their good biocompatibility,
low toxicity and reasonable price. In addition, unlike the Au-mediated materials, the
p-type semiconductor CuS possesses a d-d transition band showing NIR absorption (700–1100 nm) and, thus, does not depend on the dielectric constant
32
C. A. Ferreira et al.
Upconversion NPs (UCNPs) are a relatively new class of nanomaterials that have
been studied for biological applications. UCNPs have numerous features that make
them well-suited for therapeutic and diagnostic applications. First, their unprecedented frequency conversion capability is commonly absent in traditional fluorophores [146]. During the upconversion process, the trivalent lanthanide ions, when
embedded in a proper inorganic host lattice, sequentially absorb multiple photons in
order to produce higher energy anti-Stokes luminescence [147]. In a simpler
manner, when UCNPs are excited by a NIR source (e.g., 980 nm), they emit
higher-energy photons in the ultraviolet (UV) to NIR range. Furthermore, they
present other several advantages such as negligible autofluorescence background,
high resistance to photo-bleaching, deeper tissue penetration and less light scattering [148]. The basic structure of UCNPs consists of an inorganic host matrix
(fluorides, oxides, heavy halides etc.), a sensitizer (to enhance UCL efficiency;
Yb
3+ ) and an emitter (Er
3+ , Tm
3+ and Ho
3+ dopant ions). Doping is a commonly
used method to incorporate different functional lanthanide (Ln) ions in the NPs to
achieve multifunctional properties. UCNPs doped with Gd is an example of a tracer
agent that has been used both for MRI and optical imaging [149]. Moreover,
another theranostic application of UCNPs relies on the combination of photoluminescence (PL) imaging with other imaging modalities besides MRI, such as
computed tomography (CT) [150], SPECT [151] and PET [152]. Although only a
few studies have been reported so far, UCNPs have been radiolabeled with
68 Ga
[153],
64 Cu [154] and
124 I [155] through a chelator-based method and with
153 Sm
[156] and
18 F [157] through a chelator-free radiolabeling strategy. In an interesting
study, Rieffel et al. [158], demonstrated the ability of UCNPs as multiplexing
imaging agents, in which a hexamodal porphyrin-phospholipid-coated UCNP
(PoP-UCNP) system was developed. A simple incubation post-labeling method was
carried out by making use of the high affinity of copper for porphyrins resulting in
>80% labeling yield.
64
Cu radiolabeled PEGylated PoP-UCNPs could then be used
for fluorescence, NIR-to-NIR UCL, PET, CT, Cerenkov luminescence, and photoacoustic tomography (PAT) for in vivo lymphatic mapping (Fig. 2.7b).
Altogether, these studies show the vastly improved imaging potential of simple yet
higher-order upconversion NPs for multimodality imaging [158].
2.6.3 Copper Sulfide Nanoparticles
With different types of inorganic nanomaterials available, copper sulfide (CuS) NPs
have become an appealing choice because of their good biocompatibility,
low toxicity and reasonable price. In addition, unlike the Au-mediated materials, the
p-type semiconductor CuS possesses a d-d transition band showing NIR absorption (700–1100 nm) and, thus, does not depend on the dielectric constant
32
C. A. Ferreira et al.