1

Project Report

Summer Research Fellow-2021

(Indian Academy of Sciences, Indian National Science Academy, The national academy
of Sciences)

Advancements In Upconversion Rare Earth Element

Doped Nanophosphor Materials for Potential Applications

Submitted by
Mohammed Jasil P
(CHES171)
M. Sc. Chemistry
The Gandhigram Rural Institute, Government of India
Tamilnadu

Supervisors
Dr Raghumani Singh Ningthoujam (F.N.A.Sc)
Scientific Officer (F)
Chemistry division
Bhabha Atomic Research Centre (BARC)
Trombay, Mumbai-400085, India

&

Dr. Bheeshma P. Singh

DST Inspire Faculty
Chemistry Division
Bhabha Atomic Research Centre (BARC),
Mumbai-400085, India.

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3
 Acknowledgement
I am really grateful to Science Academies for the selection on Summer
Research Fellowship Programme Chemistry Division, Bhabha Atomic Research
Centre for allowing me to complete this project.
I am also immensely thankful to Dr Raghumani Singh Ningthoujam,
Scientific Officer (F) and Dr. Bheeshma Pratap Singh (DST Inspire Faculty
Fellow) without whose constant backup, sharp insight and relentless help this
project would have been impossible.
Finally, I am thankful to my parents who have helped me in whatever way
they can, so that I could continue my work.

Date: 28/07/2021 Mohammed Jasil P

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 CONTENT

Abstract
1. Introduction
2. Basic understanding of UCNPs
2.1.General overview on luminescence
2.2.Lanthanides and unique properties used in upconversion
2.3.Different processes in Upconversion
2.4.Upconversion in lanthanide doped materials
3. Synthesis by thermal decomposition
4. Upconverting RE doped nanophosphors in solar cells
4.1.Silicon based solar cells
4.2.Perovskite based solar cells
4.3.Dye sensitized solar cells
5. UCNPs for bio imaging and therapeutic purpose
5.1.Functionalisation and bio conjugation of UCNPs
5.2.UCNPs for invivo fluorescent bio imaging
5.3.UCNPs for therapeutic purpose
6. Upconverting RE doped nanophosphors in security purpose
7. Conclusion
8. References

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Abstract
Upconversion nanophosphor materials are interesting materials due to their ability to
convert near IR radiations to visible light. Their unique properties made them suitable to use
in a wide range of applications like - in solar cells, bio imaging in living organisms, security
purpose and anti-counterfeiting applications. The narrow photoluminescence of these
materials and their large penetration ability is exploited in bio imaging purpose. The spectral
mismatch of solar cell semiconductors with incident light is one of the vital factors causing
reduction in their efficiency. Photons which is not absorbed by the semiconductor due to their
lower energy and energy mismatch with band gap are converted to high energy photons by
nanophosphors and hence absorbed by the same semiconductor. Both upconversion and down
conversion nanophosphors are crucial in solar cells. Counterfeit products are threat to our
economy and business. Anti-counterfeiting is a difficult task in case of currencies and valuable
documents. Upconversion nanophosphors are reported potent to use as ink for such security
purposes. This review will cover theoretical insights on upconversion process of rare earth
elements doped NPs, general synthetic methods, some of the reported RE doped NPs for solar
cells, bio imaging and security purpose, challenges and future of this area.

1. Introduction
Recently luminescent materials gained noticeable momentum among researchers. It is
because of their extensive applications in many areas of our daily life which include
photovoltaic, bio-medical, anti-counterfeiting, lighting, information displays etc.1 - 2 German
physicist Wiedemann was the one who introduced the term “luminescenz”. Phosphors are the
inorganic host materials which are doped with some other ions commonly rare earth (RE)
lanthanides. Up conversion is a process in which a photon of lower energy is converted to high
energy through multiple photon absorption. Here material absorbs two or more photons and
stepwise excitation to higher level happens. It is then de-excited back to ground level by the
emission of high energy photon by summing all the absorbed photons. The ladder like energy
levels of RE elements helps in multiple photon absorption and stepwise excitation to higher
levels. Since f electrons are highly shielded by 5s and 5p electrons they are not easily vulnerable
to external conditions. These f-f transitions in RE elements are parity forbidden and f orbital is
highly shielded. Hence sharp emission and more life time of emissions are observed. This is
also called anti-stoke or non-linear emissions. Anyway the complete mechanism with proper
diagrams will be discussed in theory part. The requirement is different in different applications
of UPNCs. For example, functionalisation of surface and bio compatibility is important for bio
medical related purpose. The match of band gap of semiconductor and energy of output photon
is important when we use it in solar cells. So this review will cover three varieties of UCNPs
which can be used for solar cells, bio medicals and security purpose.

The sources of fossil fuels are limited. It is important to develop new technologies to
convert solar energy to electric energy efficiently. Solar cells are used for this conversion of
photons to electric energy.3 The maximum conversion efficiency of a single junction solar cell
is related to band gap of semiconductor.4 When a semiconductor is illuminated with a higher
energy photon than its band gap, the created high energy electrons and holes dissipate the
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excess energy as heat. This appears as thermalisation loss. Also the photons having lower
energy than the band gap are not absorbed and is not used at all. This is called spectral
mismatch.3 To solve this spectral mismatch multi junction solar cells are proposed which
connects different semiconductors in series. This could rise the efficiency twice as that of single
junction solar cells.3 Multi junction solar cells have reported for a higher efficiency of 43.5%.5
But the high cost and production difficulties are limiting use of such multi junction solar cells.
Single junction solar cells are widely used. Hence we need to think about good photon trapping
technologies. If we are able to convert the wasted photons and convert to proper energy photons
we can solve this issue. Quantum cutting, upconversion and down conversion can be used for
this. In upconversion lower energy photons are converted to high energy photons. Here we are
focusing on how upconversion nanophosphors are used in solar cells.

An important application of upconversion nanophosphor is to utilise for bio medical

applications. Mouse modelling is an important method in the invention of a drug, new diagnosis
paths, treatment etc. Computed tomography, ultrasound imaging, magnetic resonance imaging
is used for imaging in vivo applications. Fluorescence imaging in small animals such as mouse
and rats are effective for tracking living systems.6 Florescent material is better to target desired
bio molecules. The conventional materials used for this purpose are single photon absorbing
materials in which they are excited by a single high energy photon. This use of high energy
photon causes cell damage and they show lower penetration depth in living systems.7 RE (rare
earth) doped upconversion nanophosphor materials are used to overcome these limitations to a
greater extent. They are used for imaging tumour cells, lymphatic nodes and vascular imaging
in mouse models.7 Here we will focus on upconversion nanophosphor materials and their
various applications in above mentioned areas.

Another vital application of these materials are developing security ink for anti-
counterfeiting applications.8 Anti-counterfeiting techniques utilised to preserve vital
documents or currency to be safe. The inks used for this purpose will be unique and it is easy
to identify the original product from a group of its fake copies. The unique emissions from
lanthanide ions and such materials are used as a finger print emissions in security purpose.9
Here we will discuss about some of recently reported such materials for security purposes.

In this short review, we will cover the basics of upconversion RE doped nanophosphors,
general synthesis protocols, recently reported materials for solar cells, bio medical applications
and security purposes, challenges and issues to be addressed.

2. Basic understanding of UCNPs

2.1. General overview on luminescence
When a radiation of suitable frequency incident on a molecule causes excitation of electrons
and emits radiation when it comes back to ground energy level is called photoluminescence.10
Apart from photoluminescence there are other luminescence methods based on how excitation
happens. They are thermoluminescence (emission of light upon heating), electroluminescence
(shows gases under electric potential), and chemiluminescence (during chemical reactions). By
Frank-Condon principle, these electronic excitations are so fast than the vibrational movement
of the nuclei, that means nuclei do not change their position during absorption.10 There are a

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lot of ways through which excited electrons can come back to ground state. In solids absorbed
energy can be emitted by vibration or as heat or by involving in a chemical reaction
(photochemical reactions) but only radiative decay can cause photoluminescence. Here the
absorbed energy emits as photon. There are two different mechanisms in photoluminescence
called as fluorescence and phosphorescence.11-10 The radiation emitted during transition from
triplet to singlet, that is levels of different multiplicity is phosphorescence and between same
multiplicity levels called as fluorescence.12 The frequency of emitted photon during
fluorescence will be lower than that of incident light. This difference is termed as stokes shift.
Upconversion process is nonlinear anti-stoke phenomenon in which low energy input photon
is converted to high energy output photon via multi photon absorption process. The emission
happens after releasing some of the energy in the form of vibrations. Triplet state has lower
energy than the corresponding singlet states. Phosphorescence persists even after the removal
of illuminating agent.12

2.2. Lanthanides and unique properties used in upconversion

Lanthanides are the 4f block elements located at the bottom of periodic table and the
elements range from La (57) to Lu (71). The f orbitals in lanthanides are highly shielded by 5s
5p 6s and placed inside the core, therefore the crystal field effects are very less in them
compared to d block orbital splitting. Hence the spectra showed by free metal ions are almost
similar to that of spectra showed in presence of ligands. Since energy levels of lanthanides are
not splitting, they show sharp emission characters. The anti-penultimate f sub shell is well
shielded by completely filled s and p subshells so their optical properties cannot be altered by
host. Lanthanides show weak f-f transition. These 4f-4f transitions are parity forbidden hence
they give long lifetime for emission and relatively small absorption cross section. Hence RE
elements such as Er3+, Tm3+, and Ho3+ ions are used as activators in host matrix. The other
thing is that we can’t use a large concentration of activator ion. Large activator concentration
may result in cross relaxation and less efficiency since activator ions come closer
(concentration quenching). Even though the energy levels of lanthanides are independent on
the host materials, their phonon frequency plays a crucial role. The non-radiative decay become
significant if phonon frequency of host is high. This can be solved by selecting suitable host.13

Lanthanides show very less crystal field splitting than actinides. It is due to 5f orbital is
more vulnerable to ligand environment than 4f orbital. Hence lanthanides have more sharp
emission lines compared to actinides. It is a limitation that higher lanthanide dopant
concentration is reducing efficiency of upconversion so efficiency is low because of low
absorption cross section and low dopant concentration. To overcome this a sensitizer is usually
doped to host matrix along with activator. Most commonly doped sensitizer is trivalent Yb3+.
It has a single excited 2F5/2 state and energy gap between ground state and this excited state
matches with most of the activator ions. It also has a large absorption cross section compared
to other activator ions.

In general, an upconversion nanophosphor contains a host matrix which holds activator

lanthanide ions and sensitizer which is usually Yb3+. Activator is responsible for emission and
sensitizer increases absorption cross section by transferring energy to activator. This is ETU
(energy transfer upconversion) process which will discuss in coming sessions.

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 2.3. Different processes in Upconversion
Through multiple absorption of photons, the conversion of lower energy input photons to
high energy output photons is called upconversion. It is anti-stoke non-linear process. It can be
classified to three main classes. 1. Excited state absorption (ESA), 2. Energy transfer
upconversion (ETU) and 3. Photon avalanche (PA). In these mechanisms metastable energy
sates help to populate higher excited state by continuous excitation process.3 Ground state
excitation happens from G to metastable state (E1) by an incident photon. Photon management
is more feasible because of the presence of ladder like energy levels in lanthanides. Then again
excites to E2 level from there the emission happens. This process is ESA figured in Fig. 1.
ETU involves neighbouring ion. Transfer of absorbed energy from one ion to other and finally
populate E2. PA uses cross relaxation process to populate higher level. In PA, E1 level of
second ion is populated by ground state absorption (GSA) then E2 level is populated. Cross
relaxation results the population of E1 states of both ions then first ion transfers its energy to
second ion to populate E1 level and closes the cycle. In effective E1 state of both ions will be
populated. That is by interaction of second ion in E2 state with ground state first ion E1 state
get populated. By repeating this process continuously E2 of one of the ions get populated and
causes strong upconversion emission.

2.4.Upconversion in lanthanide doped materials

The nanophosphor generally contains three major components, one host material, a
lanthanide dopant as activator with ladder like energy levels and a sensitizer(Fig. 2).14 The role
of host material is to keep dopants in appropriate distance. The general electronic configuration
of lanthanides is 4fn 5s2 5p6. Partially filled anti penultimate f shell is the reason for unique
emission properties. This 4f-4f transition is forbidden and hence probability is less but gets a
long lived excited states. So there is a chance to excite it again to higher excited state. From
there upconversion emission happens.
Even though the emission can be increased by adding certain amount of dopant to host,
this in turn results increase in cross relaxation and decreases efficiency.3 To increase the
efficiency of absorption, a sensitizer which can be doped in the host material. Selection of host
material is crucial. It determines the distance between doped ions. The host must have less
phonon frequency to reduce non radiative losses. Commonly used hosts are NaYF4, NaYbF4,
NaGdF4, NaLaF4, LaF3, etc. Fluorides are most common host materials due to lower phonon
frequency of ~350cm-1 and high stability.7

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 E2 E2 E2

E1 E1 E1 E1 E1

G G G G G
Ion1 Ion1 Ion2 Ion1 Ion2
ESA ETU PA

Fig. 1. Principal upconversion processes in lanthanide doped nanomaterials.

1
D2

2
25 H9/2
4
4
F3/2
1 F5/2
G4 4
F7/2
20 2
H11/2
4
S3/2
3 4
3 2
F F9/2
15 F3
E/(10 cm )
-1

3 4
H4 2
I9/2
3

F5/2 4
10 I11/2
3
H5
4
3
F4 I13/2
5

0 3 2 4
I15/2
H6 F7/2
3+ 3+ 3+
Tm Yb Er

Fig. 2. Energy transfer mechanisms showing the UC processes in Er3+, Tm3+, and Yb3+-
doped crystals.

3. Synthesis by thermal decomposition

Here decomposition of organometallic precursor in high boiling point organic solvents
in presence of long chain surfactants happens. This process is carried out at a high temperature
of 300-3500C. Commonly used organometallic precursors are metallic triflouroacetate salts,
rare earth oleates and surfactants are oleic acid, oleylamine etc. Mai et al reported high-quality
cubic (alfa-phase) and hexagonal (beta-phase) NaREF4 (RE: Pr to Lu, Y) nanocrystals
(nanopolyhedra, nanorods, nanoplates, and nanospheres) and NaYF4:Yb,Er/Tm nanocrystals
(nanopolyhedra and nanoplates) via the co-thermolysis of Na(CF3COO) and RE(CF3COO)3 in

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oleic acid/oleylamine/1-octadecene solvents.15 TEM images are given in Fig. 3. Alfa phase is
thermodynamically unstable than beta. More transitions are observed in beta.

Shun Yi and colleagues reported upconversion fluorescent hexagonal phase

NaYF4:20%Yb,2%Er and NaYF4:20%Yb,2%Tm which is synthesized by decomposition of
metal acetates in oleylamine at 330°C.16 TEM images are given in Fig. 4. Li and co-workers
has reported the synthesis of NaYF4:Yb, Er/Tm hexagonal phase nanocrystals by using
trichloride salt of rare earth elements, NaOH and NH4F.17 They got a more precise nanocrystals
of uniform size. In this particle formation were done by Ostwald ripening mechanism at 3000C.

Very recently Joshi et al reported bright red emission (655 nm) from monodispersed
NaErF4:0.5%Tm@NaYF4:20%Yb nanocrystals (core@active shell) through thermolysis.18. In
this typical synthesis they used metal acetate and oleic acid for thermolysis. The core consists
of Tm3+ doped NaErF4 nanoparticles, NaErF4:0.5%Tm (C-NPs). Through three photon
absorption electronic transition in Er3+ in host matrix is responsible for emission at 655 nm.
TEM images of core@inactive shell NaErF4:0.5%Tm@NaYF4 (CS-Y-NPs) and core@active
shell NaErF4:0.5%Tm@NaYF4:20%Yb (CS-Yb NPs) are given in Fig. 5.
e f

g h
g h
e
Fig. 4. TEM image of the well-dispersed
NaYF4:20%Yb,2%Er nanocrystals at a
Fig. 3. TEM images of alfa-NaNdF4 (a), alfa-NaEuF4 magnification of 50000×. b) TEM image of
(b), alfa-NaYF4 (c), alfa-NaYbF4 (d), beta-NaYF4 NaYF4:20%Yb,2%Er nanocrystals at a higher
nanorods redispersed in toluene/hexane (1:1) (e) and magnification of 150000×. Reproduced with
in toluene/hexane/ethanol (1: 1:0.48) (f), of beta- copyright permission from ref. 16.
NaYF4 nanoplates (g), of beta-NaNdF4 nanorods (h).
Reproduced with permission from ref. 15. Copyright
{2021} American Chemical Society.

Fig. 5. a) Core NaErF4:0.5%Tm (scale bar 50 nm), (b)

Core@Active Shell NaErF4:0.5%Tm@NaYF4:20%Yb (
scale bar 200 nm) and (c) CS-Yb-sil-NPs (Silica Coating)
(scale bar 50 nm). Reproduced with permission from
ref. 18. Copyright {2021} American Chemical Society.

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4. Upconverting RE doped nanophosphors in solar cells
Solar cells are photovoltaic devices that convert photons to electric power. Solar cells are
the energy source of future hence numerous works are carried out in different dimensions to
develop efficient cells. Silicon solar cells are highly used systems, but they are expensive. Thin
film solar cells are cost effective but their toxicity and lower efficiency is a problem to be
addressed. Dye sensitized solar cells or perovskite based solar cells are not commercialised
widely but are efficient and is in beginning stage. The band gap of semiconductor used in a
solar cell determines its efficiency. As mentioned in introduction part the use of up or down
conversion materials can help to overcome spectral mismatch in solar cells. Here we will
discuss recent developments in RE doped upconversion nanophosphors in silicon based,
perovskite based and dye sensitized solar cells.

4.1.Silicon based solar cells

Er 3+ and Ho3+ has widely used as activator for crystalline silicon (c-Si) based solar cells
to improve efficiency. The ground state absorption of Er 3+ lies 1480-1580 nm (4I15/2 to 4I13/2
transition).3 The upconversion emission bands of Er 3+ are: 4I11/2 - 4I15/2 (980 nm), 4I9/2 - 4I15/2
(800 nm), 4F9/2 - 4I15/2 (660 nm), 4S3/2 -4I15/2 (550 nm) and 2H11/2 – 4I15/2 (525nm) Fig. 6.19 Shalav
and colleagues reported Erbium-doped sodium yttrium fluoride NaYF4:Er3+ up-conversion
phosphors attached to the rear side of a bifacial silicon solar cell and observed enhanced
absorption in NIR region.19 An external quantum efficiency of (2.5±0.2)% observed under 5.1
mW laser excitation at 1523 nm. Li and co-workers reported a novel kind of Yb3+,Er3+/Ho3+
co-doped CsGd(MoO4)2 phosphors through high temperature solid state synthesis.20 Yb3+ is
used as sensitizer which efficiently transferred energy to Er3+/Ho3+ activators. The possible
energy transfers mechanisms in Yb3+, Er3+/Ho3+ doped CsGd(MoO4)2 phosphors as shown in
Fig. 7. They found that CsGd(MoO4): 0.30Yb3+, 0.02Er3+ shown intense green light with
dominant emission peaks at 528 and 550 nm under 975 nm laser excitation. UC emission
spectra is given in Fig. 8. CsGd(MoO4): Yb3+, Ho3+ samples mainly displayed two emission
bands around 540 and 660 nm together with a negligible one at 755 nm under 975 nm laser
excitation. They observed some charge transfer phenomena and they tuned the emission which
is apt to use in solid-state lighting and displays as well as in c-Si solar energy conversion
systems. SiO2 layer containing YF3:Yb3+/Er3+ upconversion phosphors were developed by -
Jeng Ho et al.21 They reported when 30wt% YF3:Yb3+/Er3+ phosphors used the efficiency of a
bare solar cell exceeded by 13.26%. PL emission were observed at 559, 653, 669, 803, 926,
and 970nm at excitation wavelength of 1550 nm. This observation supports the phenomenon
upconversion (Fig, 9). The coupling of the upconverted photons within the active region of the
cells generated additional photo-carriers (electron-hole pairs), which enhanced the efficiency
of the cells. The efficiency improvement is as follow, 30wt% YF3:Yb3+/Er3+ phosphors
(13.26%) and 3wt% YF3:Yb3+/Er3+ phosphors (12.02%).

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 Fig. 6. UC process between two erbium Er3+
ions. Reproduced with permission from ref. 19.
Fig. 7. possible energy transfers mechanisms in Yb3+,
Er3+/Ho3+ doped CsGd(MoO4)2 phosphors. Reproduced
with permission from ref. 20.

Fig. 8. UC emission spectra of CsGd0.98-x(MoO4)2:

xYb3+,0.02Er3+ (x = 0, 0.05, 0.10, 0.15, 0.20, 0.30 and 0.40)
(a), CsGd0.70-y(MoO4)2:0.30Yb3+, yEr3+ (y = 0.005, 0.01,
0.02, 0.04 and 0.06) (b) and CsGd0.99-a (MoO4)2:
aYb3+,0.01Ho3+ (a = 0, 0.05, 0.10, 0.20, 0.30, 0.40 and
0.50) (e) upon 975 nm laser excitation. Reproduced with
permission from ref. 20.
Fig. 9. PL emission spectrum of SiO2 layer containing
YF3:Yb3+/Er3+ phosphors under excitation by a light source
with wavelength of 1550 nm. Reproduced with permission
from ref. 21.

4.2.Perovskite based solar cells

In perovskite based solar cells perovskite structured materials are used as active layer.
Recently there is a lot of works reporting in perovskite used solar cells for its efficiency
improvement and ensuring its stability. Upconversion nanophosphors can convert near IR solar
light to visible region and increase the efficiency of cell when UCNPs incorporated with solar
cells. Dongyu et al reported such an incorporation of NaYF4:Yb3+, Tm3+ phosphor with a cell
having double-layer device structure that consist of a bottom layer and a top layer of the
UCNPs, which were located next to the front (FTO) and rear (Au) electrodes.22 They witnessed
higher power conversion efficiency of 18.2% with higher long-term device stability, in
comparison with that of 15.8% from the UCNPs-free perovskite solar cells. The j-v plot of the
same is given in Fig. 10. Deng and colleagues reported bright Li(Gd,Y)F4:Yb,Er upconversion
nanophosphors efficient for perovskite solar cells.23 They found that when an optimal amount
of UCNPs (0.10wt%) used power conversion efficiency of 18.34% under AM1.5G
illumination. The j-v plot of different combinations and bare cell indicate that the performance
of cell is poorer when the wt% is below or above 0.10 (Fig. 11). Using NaCsWO3 and its near-
infrared absorption arising from the local surface plasmon resonance (LSPR) effect Feng Xu

13
et al recently developed NaCsWO3@NaYF4@NaYF4: Yb,Er incorporated perovskite solar
cells.24 They reported enhancement in upconversion luminescent intensity 124 times higher
when the amount of NaCsWO3 was 2.8 mmol %. They also got power conversion efficiency
(PCE) reaching 18.89% with that of control device was 16.01%. corresponding j-v and j-T
plots are given in Fig. 12.

Fig. 10. J–V curves of the control and Fig. 11. J-V curves of control and different
NaYF4:Yb3+, Tm3+ phosphor. Reproduced amounts of Li(Gd,Y)F4:Yb,Er. Reproduced
with permission from ref. 22. with permission from ref. 23.

Fig. 12. J−V curves (a) and J−T curves (b) of the PSCs with and without UCNPs under a 980
nm laser. Reproduced with permission from ref. 24. Copyright {2021} American Chemical
Society.
4.3.Dye sensitized solar cells
Here dye act as a sensitizer, absorbs photons and transfers excited electrons to
conduction band of semiconductor. A redox species present in solution helps to regenerate the
ground state dye again. It is found that upconversion nanophosphors can improve their
efficiency by reducing spectral mismatch. Meenakshamma and co-workers reported
LiYF4:Er3+/Yb3+ phosphors spin deposited over photoelectrodes and an improved power
conversion efficiency of 10.53% for dye sensitized solar cells.25 They used N719 and squaraine
SPSQ2 dyes for co-sensitization. The j-v characteristics of materials is given in Fig. 13. Lesly
and co-workers reported an efficiency improvement from 4.27% to 4.79% when dye sensitized
solar cell is incorporated with Y2O3:Ho3+/ Yb3+ upconversion nanophosphors.26 The j-v plot

14
provided in Fig. 14 indicate the performance of cell has improved after incorporating with
UCNPs.

Fig. 13. J-V characteristics of different
photoelectrode-assisted dye sensitized solar cells
(photoelectrodes without UC, with UC, and with
UC and cosensitization). Reproduced with
permission from ref. 25. Copyright {2021}
American Chemical Society.
Fig. 14. J-V plot of a normal dye sensitized solar
cell without UC and a DSSC with Y2O3:Ho3+, Yb3+
UC nanomaterials. Reproduced with permission
from ref. 26.

5. UCNPs for bio imaging and therapeutic purpose

Why our nanoparticles are selectively accumulating in cancerous cells than in normal cells
in targeted drug delivery? Tumour cells require more nutrients, oxygen and blood supply as
compared to normal cells. So they will develop blood vessels which is abnormal in many
factors compared to normal blood vessels. Also they lack lymphatic drainage. All these factors
contribute to abnormal fluid transport mechanisms. This forced sucking of blood towards
tumour cells also changes the size of pores in blood vessels (for leaking of nutrient and oxygen)
which favours permeation of nanoparticles to tumour areas (leaky vascular nature). Lack of
lymphatic drainage enhances retention of nanoparticles and drug in desired site. This is
collectively called enhanced permeation and retention effect (EPR). So molecules of particular
size tend to accumulate in tumour cells than in normal cells.

Mouse or rat models for small animal imaging plays a vital role in diagnosis and treatment
of humanly diseases. Fluorescence imaging plays a crucial role in tracing anatomical and
physiological features of living systems. The quality of this image depends on the fluorescent
probes used. Since conventional fluorescent probes such as semiconductor quantum sots,
organic dyes, etc. are causing cell damage, low signal to noise ratio and low penetration in
biological systems, there is a need of new fluorescent probes which offer better penetration
depth, high signal to noise ratio and low cell damages. Since NIR excitation is not so harmful
to cells UCNPs which absorb NIR has an advantage. Synthesizing hydrophobic NPs and then
modifying it to hydrophilic one is employed here. Unlike we did in solar cell applications we
need to functionalize and bio conjugate the UCNPs to be applied in bio systems. It should have
suitable size and shape, good dispersion in aqueous solutions, surface modification with
functional groups such as carboxyl (–COOH), amino (–NH2), maleimide (MA) groups for

15
biocompatibility and bio conjugation at preferred sites and low toxicity.7 Before applying as
synthesized UCNPs in biological systems we have to functionalise and modify the surfaces.

5.1.Functionalisation and bio conjugation of UCNPs

Generally surface modifications are chemisorption since it gives stronger and stable
surface ligands compared to physisorption. The efficient conjugation of biomolecules in cells
depend on how the surface of nanoparticle is modified with a ligand. Ligand is the functional
group in modified surface of nanoparticle which is going to bind with biomolecule. Since most
of the synthesized particles are water insoluble or less soluble we have to solubilize them by
surface modifications. One of the most widely used method for surface functionalization is
silica coating.27 Silica coating has advantage of very less non intended interaction with
biomolecules, highly stable and water soluble over organic coatings. It is an inorganic surface
modification. Silica-Coated Ln3+-Doped LaF3 Nanoparticles reported by Sivakumar et al.28
They synthesized silica-Coated Ln3+-Doped LaF3 Nanoparticles from Citrate-stabilised
LaF3:Ln3+ nanoparticles using tetraethyl orthosilicate (TEOS). Through almost similar
procedure Zhengquan and co-workers reported silica coated PVP/NaYF4 nanocrystals using
tetraethoxysilane (TEOS).29 For In-vitro Bio imaging study of
NaErF4:0.5%Tm@NaYF4:20%Yb on lung cancer (A549) and breast cancer (MCF-7) cells,
Rashmi Joshi et al made the UCNPs water soluble when coated with NH2 functionalized
silica.18 Silica-Coated Ga(III)-Doped ZnO: Yb3+, Tm3+ Upconversion Nanoparticles were
successfully tested for in-vivo bio imaging by Yuemei Li and colleagues.30 Here also silica
coating is done using TEOS. As we mentioned earlier silica coating can make our particle water
soluble and bio compactible. Now how can we functionalize this silica coated particle with
biomolecules? For this we have to link the silica coated surface with some functional groups
that can react with our biomolecule. Usually –COOH, –NH2 or MA groups are used which can
react with folic acid (FA), DNA etc. Carboxyl-terminated nanoparticles can react with
biological molecules containing –NH2 groups, such as diamino PEG, antibodies, streptavidin,
FA-chitosan, DNA. The amine modified NPs can further conjugate with FA, antibodies, DNA
etc. Joshi et al has used 3-amino propyl trimethoxy silane for the introduction of NH2 group.18
They could further conjugate it with FA for bio imaging purpose of tumour cells.

Rashmi et al has made nanophosphor water dispersible by coating with silica and then
with amine.18 Amine coated UCNPs are then functionalised by folic acid. An amide bond is
formed between –NH2 group in surface amine and –COOH group of folic acid. EDC-NHS
method is used for activating FA to bind with –NH2 group. N-(3-dimethylaminopropyl)-N’-
ethylcarbodiimide (EDC) along with N-hydroxysuccinimide (NHS) accelerates this coupling
rate and efficiency.31 EDC activates carboxyl group on FA to bind with primary amine group
which is on the surface of UCNPs to form amide bond. NHS on reaction with carboxyl group
forms an amine reactive ester to couple with amine group. The intermediate formed by NHS is
more stable than that of produced by EDC alone.31

Another most widely used method for functionalization of hydrophobic UCNP is

Ligand exchange method. Here the surfactant species which is not water soluble are exchanged
with desirable ligands or polymers which forms shells.27 But the procedure for ligand exchange
is complicated and aggregation of nanoparticles also observed. Veggel et al has reported oleate

16
exchange by PEG-phosphate ligand and synthesized water dispersible NaYF4: Yb,Er/Tm
nanoparticles.32 There are several recently developed methods which is not mentioned here.
Ligand oxidation method is also used by oxidising the carbon–carbon double bond of the oleate
or OM using Lemieux−von Rudloff reagents, ozone or 3-chloroperoxy-benzoic acid. The
activated group by oxidation show an enhanced water solubility.33

Peptide linked UCNPs are also reported for tumour targeting applications. Peptides
show better cellular uptake and penetration in animals. Yu et al developed CTX peptide
(chlorotoxin) mediated NaYF4: Yb,Er/Ce UCNP for visualising tumour in animals.34 CTX is
isolated from scorpion Leiurus quenchestriatus. CTX has reported to target cancerous cells
especially brain tumour (glioma). Low toxicity of such peptide linked UCNPs are impressive.

5.2.UCNPs for invivo fluorescent bio imaging

For bio imaging the optical window of biological tissues are in the range of 700-
1100nm for excitation and 600-900nm for emission.35 For Er3+ doped nanoparticles emission
bands appear at 540 and 650nm. Among them 650nm belongs to optical window of biological
tissues. In case of Tm3+ emission is at 800nm under 980nm excitation and also both excitation
and emission band matches with optical window of biological tissues. So Tm3+ is best for bio
imaging purpose. Bio imaging require the understanding of bio distribution of UCNPs.
Inductively coupled plasma atomic emission spectroscopy (ICP-AES) helps to identify the
lanthanide ions in different bio systems. But here we can track the bio distribution of UCNP
material by its luminescent property. The bio distribution study of polyacrylic acid coated
UCNP (PAA-coated NaYF4: Yb,Tm) was conducted by Xiong et al using nude mice.36 The
mice were injected with 15mg/Kg of PAA-UCNP for long term observation. After injection
mice were anesthized, sacrificed and imaged using an imaging system. The analysis of signal
originated from mice body indicated that it was from spleen and liver. No trace of UCNPs in
blood indicates its timely circulation. After 14 days of injection no presence of UCNPs in
spleen and liver recorded, but it was present in intestine. This results were further confirmed
by ex-invivo and ICP-AES studies. This type of bio distribution studies helps us to know how
our UCNP is up taken and excreted by living system.

Because of the high stability, conjugation with variety of bio molecules, low
immunogenic activities and high affinity of folic acid (FA) towards over expressed folate
receptors (FR) in tumour cells, FA or modified FA labelled UCNPs are widely applied in invivo
tumour imaging. NaYF4:vYb,Er UCNPs were reported for targeted Hela tumour imaging by
Xiong et al.37 After injection of FA-UCNPs to a Hela tumour bearing mice, upconversion
emission was observed in 24 hours and no emission observed in case of NH2-UCNP injected
mice. It indicates the targeting ability of FA-UCNPs towards Hela tumour cells. Along with
FA labelled UCNPs, peptide and antibody labelled UCNPs also have reported for tumour
imaging. Lymphatic imaging is also done for tumour cells imaging purpose. Because secondary
malignant growths can be carried through lymphatic drainage as well. Multi-colour lymphatic
imaging using UCNPs were carried out by Kobayashi and colleagues using NaYF4:Yb,Er and
NaYF4:Yb,Tm.38 Here the green light could only observe after removal of skin during surgery
and NIR observed before that. Both could clearly target the lymph node, but for Yb3+ sensitized

17
UCNPs excitation wavelength of 980nm is also absorbed by water and causing heating effect.35
Hence Nd3+ sensitized UCNPs are introduced which has a 808nm excitation wavelength.39

5.3.UCNPs for therapeutic purpose

Apart from conventional chemotherapy or radiotherapy or surgery for treatment of
cancer photodynamic therapy (PDT) is grabbing attention of scientific world. It is used to kill
cancerous cells when a photosensitizer is excited to produce reactive oxygen species (ROS)
like singlet oxygen (1O2), which is toxic to cells. The penetration ability of UCNPs can be used
here for PDT. The main component of PDT is photosensitizer called PDT drug. An efficient
PDT drug should be able to specifically target the diseased cells, effective production of ROS,
less toxicity etc.40 The PDT efficiency of NaYF4:Yb3+,Er3+ with merocyanine 540 (M-540) as
photosensitizing molecule is studied by Zhang et al.40 The overlap between emission of
NaYF4:Yb3+,Er3+ and absorption of M-540 is used here. However, the efficiency of PDT is still
low and is expected to find better ways to solve this.

Another non-invasive cancer therapy is PTT (Photothermal therapy). Here

photothermal agents absorb light energy and convert it to heat energy and thermally damages
tumour cells. It is achieved by linking UCNPs with photothermal agents. Graphene oxide,
CuxS, Au and Ag are used as photothermal agents by combining with UCNPs. In case of Au
or Ag surface plasmon resonance (SPR) is operating. Metals have free conducting electron
cloud called plasmon. When appropriate EM radiation having suitable frequency (NP size
smaller than wavelength) incident on it, plasmon will join in resonance with applied frequency.
It causes excitation of electrons and successive non radiative transition as heat energy. This
thermal heating above 40oC is capable to kill cancerous cells. The 542nm emission of Er3+ is
capable for SPR with Au NP. Liang Cheng and colleagues have developed Au linked UCNPs
along with Fe2O3 nanoparticles by layer-by-layer self-assembly for bioimaging and PTT.41
Photothermal ablation of cancerous cells by using Ag as photothermal agents also reported.
Dong et al reports NaYF4: Yb,Er@Ag composite for PTT and observed a lower mortality rate
of tumour cells than Au particles.42

Another important method used to target and treat cancer cells is using
superparamagnetic nanoparticles through hyperthermia. Hyperthermia is the process of
overheating and killing of the cells (41 – 42oC). The heat loss in magnetic nanoparticles during
magnetisation can be used for hyperthermia applications. Magnetic nanoparticles can locate in
cancerous cells alone using external magnetic field. Magnetic hyperthermia is common in iron
oxide particles and it is heated by external altering magnetic field which causes heat loss by
continuous magnetisation. When such a high frequency alternating magnetic field applied on a
superparamagnetic nanoparticle, the magnetisation by gradual alignment happens through
‘relaxation’. Relaxation has two mechanisms, Brownian relaxation (rotation of particle as a
whole to align in the direction of field, when particle size less than 10nm) and Neel relaxation
(rotation of magnetic moment in each particle, for larger particles). Higher hearing can be
achieved by Brownian relaxation. Magnetic materials with curie temperature 41 – 45oC is used
for hyperthermia applications. In superparamagnetic material, instead of each atom
independently influenced by external field the magnetic moment the entire particle aligns with
external field. As the temperature increased by hyperthermia the material will be in

18
paramagnetic state (thermal agitation) and hence heating action will automatically reduce. Here
for superparamagnetic material for hyperthermia application, particle size matters. The size
decides Brownian relaxation and heating effect. Sharma et al reported water dispersible Fe3O4
nanoparticles (7nm) for in vitro hypothermia treatment of breast carcinoma cells.43 Hybrid
formation of iron oxide particles with UCNPs can give bio imaging and therapeutic
applications. Ramaswami and co-workers have successfully synthesized such a hybrid. In this
the used YVO4:Ho3+/Yb3+ nanophosphors coated with PEG and incorporated Fe3O4 for
hypothermia applications.44 YVO4 host has low phonon frequency hence less non-radiative
decay. When a radiofrequency of 280 kHz and 310 Oe magnetic field applied for different
concentrations of Fe3O4@ YVO4:Ho3+/Yb3+, it was observed that a temperature of ~42oC
achieved for 4mg/ml within 10 minutes whereas 5mg/ml system reached within 7 minutes.
When K+ co-doped to above nanophosphor luminescence intensity increased. YVO4:Ho3+-
Yb3+-K+ was synthesized by Ramaswami and colleagues and found that 4mg/ml composition
reached 42oC in 13 minutes, 5mg/ml within 9 minutes.45 K+ ion modify electric field
environment and lattice strain in host. It enhances the luminescence of activator. Introduction
of K+ distorts the crystal lattice and produces an asymmetric environment. This enhances the
radiation transition probability. This is evident from recording emission from various
concentrations of K+. Emission intensity raised as K+ % increased and optimised at 7% K+ then
decreased afterwards.

6. Upconverting RE doped nanophosphors in security purpose

The luminescent ink using for security purpose should have high stability, low cost and
availability of ink medium, high luminescent intensity, convenience to print and adhesive
property to different surfaces. UCNPs are extremely stable in different environmental
conditions compared to organic dyes or quantum dot security inks.18 These materials upon
excitation can give different fluorescence depending on the doping material. This unique
property is exploited as a security ink. In application level choice of ink medium is important.
The ink medium should poses required viscosity so that ink will stick to surfaces. Also some
volatile medium such as toluene causes ‘coffee ring effect’ due to faster evaporation from edge
of drops. So a high boiling point medium is used. Rashmi et al has successfully used bright red
upconversion of NaErF4:0.5%Tm@NaYF4:20%Yb for ant counterfeit applications.18 Xie and
co-workers synthesized hexagonal-phase NaYF4: Ln3+ (Ln3+ = Er 3+/Tm3+, Yb3+/Er3+, and
Yb3+/Tm3+ - red-green-blue luminescence) upconversion hollow micro tubes hydrothermally
and used for smart anti-counterfeiting application.46

7. Conclusion
This review has emphasized a short introduction about lanthanides and their unique
properties, discussion on energy transfer processes in UCNPs with proper diagrams. The
special characteristics of UCNPs compared to quantum dots and organic dyes also discussed.
Some of the applications of UCNPs in solar cells, biomedical and security purpose is discussed
in detail. Relevant literature has sited.
More works have to be done to exploit nanophosphors in other challenging areas like
photocatalytic CO2 reduction, artificial photosynthesis, water splitting etc. Nanophosphors are

19
used as spectral converters in solar cells. So they can also be used in possible photo catalysis
processes to improve efficiency of semiconductor catalyst used. Still there is a lot of challenges
faced by these UCNPs in solar cells. The efficiency of upconverting material used in solar cells
in still low. Use of core shell structures and impurity doping is some of the methods to improve
efficiency. The attractive application of UCNPs are in biomedical field. We discussed the
functionalisation of particles, bio conjugation and some of the reported UCNPs for bio imaging
and therapeutic purposes. This is a hopeful area for targeted cancer therapy. Then UCNPs as
security ink especially for anti-counterfeiting has discussed. More studies have to be done for
further improvement in efficiency and bright intense emissions of nanophosphors.

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