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[×ÊÔ´] Chemical Reviews×îÐÂ×ÛÊö£ºUpconversion Nanoparticles

Upconversion Nanoparticles: Design, Nanochemistry, and Applications in Theranostics

Theranostics is a concept of integrating imaging and therapy
into a single platform for use in the next generation of
personalized medicine to meet the challenges in modern health
care.The diagnostic role of theranostic agents reports the
presence of a disease, its status, and its response to a speci fi c
treatment, while the therapeutic role of the agent can be
implemented in several formsi) The fi rst is imaging-guided
surgery for tumor resection and postsurgery evaluation.
Intraoperative visualization of diseased areas is important for
precision surgery, as the location of the tumor may change after
presurgical imaging and during resection.
Furthermore,postsurgical assessment is valuable in ensuring complete
removal of the diseased sections. (ii) The second is delivery
or release of therapeutic entities to the intended site. The
delivered entities can be small molecule chemotherapeutics
(such as cisplatin, doxorubicin, and paclitaxel), biologics (such
as protein drugs and antibodies), gene products (DNA, siRNA,
and miRNA), nanotherapeutic agents, and even cells.The
release/therapy can be light-activated such as in photodynamic
therapy (PDT) for destruction of the tumor or heat activated
by nonradiative conversion of absorbed photon energy into
heat such as in photothermal therapy (PTT)£¬
which disrupts the structure of the cells and shrinks the tumor volume.
(iii)The third is disruption of a cellular or metabolic pathway.
An occupation of speci fi c cell surface receptors by introduced
theranostic agents with appropriate chemistry can disrupt cell
regulation, producing a therapeutic e ff ect
Theranostics o ff ers an opportunity to embrace multiple techniques to arrive at a
comprehensive imaging/therapy regimen. Incorporation of
therapeutic functions into molecular imaging contrasts plays a
pivotal role in developing theranostic agents
Molecular imaging using photoluminescence (PL) spectroscopy is an
important technique in biochemistry and molecular biology. It
has become the dominant method revolutionizing medical
diagnostics, bioassays, DNA sequencing, and genomics.It
can be used to study a wide range of biological specimens, from
cells to ex vivo tissue samples, and to in vivo imaging of live
objects; it can also cover a broad range of length scale, from
submicrometer-sized viruses and bacteria, to macroscopic-sized
live biological speciesThus, PL imaging provides a
powerful noninvasive tool to visualize morphological details in
tissue with subcellular resolution. However, the imperfect
optical properties of conventional PL imaging agents and the
challenge in incorporation of therapeutic functions onto them
have severely limited their abilities for use in theranostics.

CONTENTS
1. Introduction B
1.1. Upconversion Nanoparticles (UCNPs) C
1.2. Upconversion Mechanisms E
1.2.1. Excited-State Absorption E
1.2.2. Energy Transfer Upconversion E
1.2.3. Cooperative Sensitization Upconversion E
1.2.4. Cross Relaxation E
1.2.5. Photon Avalanche E
2. Architecting Upconversion Nanoparticles with
High E ffi ciency F
2.1. Selection of Novel Host Materials F
2.2. Tailoring Local Crystal Field F
2.3. Plasmonic Enhancement G
2.4. Engineering Energy Transfers within Lan-
thanide Dopants H
2.5. Suppression of Surface-Related Deactiva-
tions H
2.5.1. Enhancing Upconversion Photolumines-
cence with a Homogeneous Core/Shell
Structure I
2.5.2. Enhancing Upconversion Photolumines-
cence with a Heterogeneous Core/Shell
Structure I
2.5.3. Enhancing Upconversion Photolumines-
cence with an Active Core/Active Shell
Structure J
2.6. Future Directions of Improving Upconver-
sion E ffi ciency J
3. Upconversion Emission Color Tunability K
3.1. Multicolor Emission Using Di ff erent Activa-
tors or Combinations L
3.2. Tuning Upconversion Emission by Interpar-
ticle Energy Transfer or Antenna E ff ect L
3.3. Tuning Upconversion Emission through
Energy Migration L
3.4. Tuning Upconversion Emission Using Cross-
Relaxation Processes M
3.5. Tuning Upconversion Emission Using Core/
Shell Structures N
3.6. Tuning Upconversion Emission Using Li-
gand E ff ects N
3.7. Tuning Upconversion Emission Using Size-
and Shape-Induced Surface E ff ects N
3.8. Tuning Upconversion Emission Using FRET
or LRET O
3.9. Future Opportunities for Tuning Upconver-
sion Emission Q
4. Nanochemistry for Controlled Synthesis S
4.1. Thermolysis Strategy S
4.1.1. Thermolysis in Oleic Acid and Octade-
cene S
4.1.2. Thermolysis in Oleic Acid/Oleylamine,
Oleic Acid/Oleylamine/Octadecene, and
Oleylamine Solvents S
4.1.3. Thermolysis in Oleic Acid/Trioctylphos-
phine Oxide/Octadecene T
4.2. Ostwald-Ripening Strategy T
4.3. Hydro(solvo)thermal Strategy T
4.4. Hierarchical Core/Shell Upconversion Nano-
particles U
4.5. Future Opportunities for Synthetic Chem-
istry V
5. Nanochemistry for Surface Engineering V
5.1. Ligand Exchange V
5.2. Ligand Removal W
5.3. Ligand Oxidation W
5.4. Layer-by-Layer Assembly W
5.5. Surface Silanization W
5.6. Amphiphilic Polymer Coating X
5.7. Bioconjugation Chemistry X
5.8. Future Opportunities for Surface Engineer-
ing Y
6. Biosensing and Bioassays Y
6.1. Temperature Sensing in Cells AA
6.2. Biosensing of Metal Ions AA
6.3. Biosensing of Gas Molecules AA
6.4. Bioassays AB
6.4.1. Heterogeneous Assay AB
6.4.2. Homogeneous Assay AC
6.5. Future Opportunities for Biosensing and
Bioassays AD
7. High Contrast Bioimaging AE
7.1. In Vitro and In Vivo Toxicity Assessment AE
7.2. Cellular Imaging AF
7.3. Whole-Body Photoluminescent Imaging AG
7.3.1. Passive Imaging AG
7.3.2. Active Targeting AH
7.3.3. Deep Tissue Imaging AH
7.4. Optical Tomography AI
7.5. Multimodal Imaging AJ
7.5.1. Upconversion Photoluminescence and
Magnetic Resonance Imaging (MRI) AJ
7.5.2. Upconversion Photoluminescence and
X-ray Computed Tomography (CT) AL
7.5.3. Upconversion Photoluminescence and
Positron Emission Tomography (PET) AL
7.5.4. Upconversion Photoluminescence,
Magnetic Resonance Imaging (MRI),
and Positron Emission Tomography
(PET) or X-ray Computed Tomography
(CT) AM
7.6. Future Directions for High Contrast Bioimag-
ing AN
8. Application of Upconversion Nanoparticles in
Drug Delivery and Therapy AO
8.1. Drug Delivery AO
8.2. In Vitro and In Vivo Photoactivations AP
8.3. Upconversion-Guided Photothermal Ther-
apy AR
8.4. Upconversion Photodynamic Therapy AR
8.5. Future Directions for Therapeutics AS
9. Concluding Remarks AS
Author Information AT
Corresponding Authors AT
Notes AT
Biographies AT
Acknowledgments AU
References AUChemical Reviews×îÐÂ×ÛÊö£ºUpconversion Nanoparticles
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