Based on the anti-Stokes shift luminescence mechanism and NIR light absorption, transition metal-doped semiconductor nanoparticles and lanthanide ion-doped
nanoparticles (upconversion nanoparticles) offer high-resolution whole-body imaging with deep tissue penetrations (up to several ~cm). Interestingly, persistent
luminescent nanoparticles were found to be excited (either by ex vivo or in situ)
with no input energy during in vivo imaging resulting in minimal tissue
autofluorescence. Nano-diamonds can also facilitate background-free imaging by
time gating due to the longer emission lifetime than that of biological tissue.
Additionally, some optically transparent inorganic nanomaterials (e.g., calcium
phosphate, silica) have been used as a host matrix to encapsulate organic
fluorophores to improve their physiological stability for longer in vivo imaging
despite the fact they do not possess the intrinsic luminescence.
However, despite all of these considerable advances in inorganic fluorescent
nanomaterials, there are still several challenging issues that need to be resolved.
The unique optical properties of inorganic nanomaterials are generally dependent on
their size, shape, and compositions, and thus large-scale synthesis is needed to
maintain the uniformity of the nanoparticles between batches. In addition, due to
the metal-induced toxicity, the potential safety issues of inorganic nanoparticles
should be addressed for further clinical trials. An effective strategy is to make
nanomaterials biodegradable into nontoxic byproducts (e.g., porous silicon
nanoparticles) or nanomaterials that are solely composed of benign elements (e.g.,
silicon, silver, gold, calcium phosphate, carbon analogue) to exert less systemic
toxicities. Renal clearance through urine can minimize the exposure of body to
nanomaterials; likewise Au nanoclusters (<2 nm) or QDs with renal cutoff size
(<5.5 nm) were found to be easily filtered by the kidneys. However, these changes
can lead to trade-offs for the intended applications, and it is critical to tailor
nanomaterials to balance between safety concerns, scale-up synthesis, and sensitivity/resolution that needs to fulfill the specific medical goal.
Compliance with Ethical Standards
Funding: This work was supported by the NIH R00 117048 and HL 137187.
Conflict of Interest: The authors declare that they have no conflicts of interest.
Ethical approval: This chapter does not contain any studies with human participants or animals
performed by any of the authors.
References
1. Alivisatos AP (1996) Semiconductor clusters, nanocrystals, and quantum dots. Science
271:933–937
2. Jaiswal JK, Mattoussi H, Mauro JM, Simon SM (2003) Long-term multiple color imaging of
live cells using quantum dot bioconjugates. Nat Biotechnol 21:47–51
3. Bruchez M, Moronne M, Gin P, Weiss S, Alivisatos AP (1998) Semiconductor nanocrystals as
fluorescent biological labels. Science 281:2013–2016
74
T. Kim and J. V. Jokerst
nanoparticles (upconversion nanoparticles) offer high-resolution whole-body imaging with deep tissue penetrations (up to several ~cm). Interestingly, persistent
luminescent nanoparticles were found to be excited (either by ex vivo or in situ)
with no input energy during in vivo imaging resulting in minimal tissue
autofluorescence. Nano-diamonds can also facilitate background-free imaging by
time gating due to the longer emission lifetime than that of biological tissue.
Additionally, some optically transparent inorganic nanomaterials (e.g., calcium
phosphate, silica) have been used as a host matrix to encapsulate organic
fluorophores to improve their physiological stability for longer in vivo imaging
despite the fact they do not possess the intrinsic luminescence.
However, despite all of these considerable advances in inorganic fluorescent
nanomaterials, there are still several challenging issues that need to be resolved.
The unique optical properties of inorganic nanomaterials are generally dependent on
their size, shape, and compositions, and thus large-scale synthesis is needed to
maintain the uniformity of the nanoparticles between batches. In addition, due to
the metal-induced toxicity, the potential safety issues of inorganic nanoparticles
should be addressed for further clinical trials. An effective strategy is to make
nanomaterials biodegradable into nontoxic byproducts (e.g., porous silicon
nanoparticles) or nanomaterials that are solely composed of benign elements (e.g.,
silicon, silver, gold, calcium phosphate, carbon analogue) to exert less systemic
toxicities. Renal clearance through urine can minimize the exposure of body to
nanomaterials; likewise Au nanoclusters (<2 nm) or QDs with renal cutoff size
(<5.5 nm) were found to be easily filtered by the kidneys. However, these changes
can lead to trade-offs for the intended applications, and it is critical to tailor
nanomaterials to balance between safety concerns, scale-up synthesis, and sensitivity/resolution that needs to fulfill the specific medical goal.
Compliance with Ethical Standards
Funding: This work was supported by the NIH R00 117048 and HL 137187.
Conflict of Interest: The authors declare that they have no conflicts of interest.
Ethical approval: This chapter does not contain any studies with human participants or animals
performed by any of the authors.
References
1. Alivisatos AP (1996) Semiconductor clusters, nanocrystals, and quantum dots. Science
271:933–937
2. Jaiswal JK, Mattoussi H, Mauro JM, Simon SM (2003) Long-term multiple color imaging of
live cells using quantum dot bioconjugates. Nat Biotechnol 21:47–51
3. Bruchez M, Moronne M, Gin P, Weiss S, Alivisatos AP (1998) Semiconductor nanocrystals as
fluorescent biological labels. Science 281:2013–2016
74
T. Kim and J. V. Jokerst