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148 CHAPTER 6 Laser-assisted cancer treatment
in vivo studies in 4T1 cells tumor-bearing mice showed a significant reduction in
tumor size after NIR laser irradiation [68].
6.4.2 Two-photon conversion guided drug release (TP-NIRSRS)
Designing NIRSRS should have some characteristic features including strong absorp-
tion in NIR region, efficient photothermal conversion, efficient drug accumulation,
and low toxicity. One of the main drawbacks of light-responsive drug release systems
is that many of these systems require high energy wavelength of UV or visible light
which have sufficient energy for activation.
As already discussed, UV light suffered from poor penetrating ability and harmful
cell toxicity. To overcome this issue, two-photon absorption nanoparticles have been
introduced characterized by absorption of two low-energy of NIR light and converting
to high-energy visible light. This high visible light energy can sensitize oxygen to pro-
duce singlet oxygen or reactive oxygen species to kill abnormal cells. NIR light used to
excite the nanoparticles lead to penetrating light to deep-seated tumors. Furthermore,
two-photon absorption nanoparticles normally possess high cross-section absorption
which has to do with efficient PDT therapy. Croissant et al. found that hydrophobic
poly(2-nitrobenzyl methacrylate) and hydrophilic polyethylene oxide had two-pho-
ton conversion potential [69] which can be used for TP-NIRSRS. In another study,
novel paracyclophane-based fluorophore nanoparticles were embedded on the pores
of mesoporous silica. The fluorophore could absorb two-photon in NIR region and
convert energy via FRET to azobenzene of valve leading to open valves through cis-
trans isomerization and releasing encapsulated drug [70]. The results demonstrated
an efficient cell death after NIR laser irradiation, while no significant cell death was
observed without irradiation. In 2017, novel nitrogen-doped carbon dots were synthe-
sized for TP-NIRSRS. Ardekaniet et al. found that their nanoparticles exhibited both
NIR responsive drug release and photothermal cell toxicity in in vitro model [71].
6.4.3 Upconverting nanoparticles guided drug release
(UP-NIRSRS)
UCNPs can convert NIR light to high-energy UV and visible light mainly made of
lanthanides. Then, this high energy can activate photochemical reactions leading to
an increase in cargo release or activate photosensitizers for PDT application. UCNPs
nanoparticles have improved the main drawback of UV sensitive nanoparticle, that
is, toxicity and poor penetration dept. Three ways have been studied to fabricate
UP- NIRSRS: (a) UCNPs and drug have been encapsulated in hydrophobic carri-
ers via hydrophobic-hydrophobic interaction. (b) Mesoporous silica-coated UCNPs
are providing large surface area for drug deposition. (c) Encapsulating of drug and
UCNPs nanoparticles in spherical carriers [71]. In 2013, Liu et al. introduced novel
UP- NIRSRS composed of NaYF4:TmYb core-shell with a coating layer of mesopo-
rous silica containing azobenzene groups. The cellular uptake was further improved