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Published in final edited form as:
Chem Soc Rev. 2013 January 7; 42(1): . doi:10.1039/c2cs35216h.
BODIPY Dyes In Photodynamic Therapy
Anyanee Kamkaewa, Siang Hui Limb,d, Hong Boon Leeb, Lik Voon Kiewc, Lip Yong Chungd,
and Kevin Burgessa
aDepartment of Chemistry, Box 30012, Texas A & M University, College Station, TX 77841-3012,
USA.
bCancer
Research Initiatives Foundation (CARIF), Subang Jaya Medical Centre, 47500 Subang
Jaya, Selangor, Malaysia.
cDepartment
of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, 50603
Malaysia.
dDepartment
of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur,
Malaysia.
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Abstract
BODIPY dyes tends to be highly fluorescent, but their emissions can be attenuated by adding
substituents with appropriate oxidation potentials. Substituents like these have electrons to feed
into photoexcited BODIPYs, quenching their fluorescence, thereby generating relatively longlived triplet states. Singlet oxygen is formed when these triplet states interact with 3O2. In tissues,
this causes cell damage in regions that are illuminated, and this is the basis of photodynamic
therapy (PDT). The PDT agents that are currently approved for clinical use do not feature
BODIPYs, but there are many reasons to believe that this situation will change. This review
summarizes the attributes of BODIPY dyes for PDT, and in some related areas.
Introduction
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Photodynamic therapy (PDT) is an emerging clinical modality for treatment of neoplastic
and non-malignant lesions. Applications of PDT require a photosensitizing drug, light, and
oxygen. A series of photochemical reactions generate singlet oxygen from the 3O2 causing
tissue damage in the regions where these three key components come together.1, 2 This is a
highly localized effect because the half-life of singlet oxygen is low (0.6 × 10−6 s).3 In
cancer treatment, PDT can destroy the vasculature surrounding tumour cells, and activates
immunological responses against them.4 The main attribute of PDT is its potential for dual
selectivity, ie preferential accumulation of photosensitizer in diseased- over normal- tissues,
and focusing light to confine damage to the targeted region.5 PDT is relatively non-invasive,
and treatments can be repeated without induction of resistance. 2
Correspondence to: Kevin Burgess.
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One of the earliest clinical PDT agents is porfimer sodium (Photofrin®), a purified
hematoporphyrin derivative. Porfimer sodium is a mixture of oligomeric porphyrin units (up
to eight) linked by esters and ethers. It has received worldwide regulatory approval in
several indications, including cancers of the esophagus, lung and bladder. Porfimer sodium
is activated by red light at ca 630 nm. Photons of this wavelength do not penetrate tissue
beyond a few millimeters, hence porfimer sodium is only suitable for superficial tumours, or
ones that can be reached via endoscopic/fiber optic procedures. Moreover, porfimer sodium
has a low absorbance at 630 nm necessitating extended irradiation from a high-energy
source, and this often leads to complications. Another disadvantage of porfimer sodium is
that it is not cleared quickly leading to post-treatment skin photosensitivity.6
Recognition of the disadvantages of porfimer sodium has inspired efforts to develop more
effective PDT photosensitizers. Desirable properties7, 8 for such agents include:
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•
low toxicity in absence of light;
•
low side-effect profiles (eg skin photosensitivity and pain after irradiation);
•
appropriate lipophilic/hydrophilic balance for selective accumulation in tumour
tissue;
•
high extinction coefficients, particularly at long wavelengths for deep tissue
penetration of light;
•
low quantum yields for photobleaching; and,
•
high singlet-to-triplet intersystem crossing efficiencies.
Table 1 lists some newer photosensitizers that have been approved for anti-cancer PDT
along with some of their salient physicochemical properties (comprehensive reviews on
these compounds have been published elsewhere).8 One of these clinically applied
photosensitizers, 5-aminolevulinic acid (ALA), is not a chromophore, but a precursor for the
biosynthesis of the protoporphyrin IX (PpIX).9 In tumours expression of ferrochelatase, the
enzyme that converts PpIX to heme, is downregulated causing accumulation of the
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protoporphyrin PDT agent.10 PpIX is rapidly cleared from the body, minimizing the risk of
skin photosensitization.11 However, ALA is hydrophilic and has limited penetration across
certain biological barriers, so a lipophilic derivative, methyl-aminolevulinic acid, has also
been developed.12 Nevertheless, the absorption spectrum for PpIX at 630 nm is similar to
porfimer sodium hence it also gives only superficial tissue penetration in PDT.
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There are some clinically approved chlorin-based photosensitizers that are similar to PpIX.
One of these, temoporfin (Foscan®), offers improved potency, less skin photosensitivity, and
a longer maximum absorption wavelength.28 However, temoporfin is so hydrophobic that it
can precipitate upon administration.29 Similarly verteporfin is activated by light at 690 nm,
clears rapidly from the body, and only generates short-term skin photosensitivity.30 This
agent self-aggregates in aqueous solution,31 hence it is applied in liposome formulations;
this mode of delivery restricts the scope of use to, so far, age related macular degeneration
caused by abnormal blood vessel growth of the retina.32 Two other clinically approved
chlorin-based photosensitizers are mono-aspartyl-L-chlorin e6 (also know as talaporfin) and
chlorin e6-polyvinylpyrrolidone. Both these PDT agents are excellent singlet oxygen
generators but have high photobleaching rates that reduce their PDT efficiencies.33
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The discussion above correctly implies that most clinically relevant PDT agents are cyclic
tetrapyrroles (porphyrins, chlorins, and bacteriochlorins).34, 35 These can be synthetically
inaccessible, and modifications to modulate their photophysical and biological properties are
correspondingly difficult. Consequently, there is interest in non-porphyrin photosensitizers
that might be made more easily.36–38 Phenothiazinium-based structures are a well-known
category of this type of PDT agent; they are easy to make but have low light-to-dark toxicity
ratios.39
A new class of PDT agents has emerged over the last decade: these are based on the 4,4difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) core. BODIPYs have many ideal
photosensitizer characteristics including high extinction coefficients, environment
insensitivity, resistance to photobleaching,40 and higher light-dark toxicity ratios41 than
phenothiazinium39 PDT agents. Several review papers have covered the role of BODIPYs as
fluorescence imaging probes,42–46 but none have focused on derivatives for PDT.
Fluorescence occurs via relaxation from singlet excited states, so high quantum yields for
fluorescence are undesirable since this means that much of the energy absorbed on
excitation does not cross to triplet states. Consequently, BODIPYs for PDT have to be
modified to depress fluorescence and enhance singlet-to-triplet intersystems crossing. This
review summarizes characteristics of selected members in this emerging class of BODIPYbased PDT agents.
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Halogenated BODIPYs
BODIPY derivatives are amenable to extensive modifications around the 4,4-difluoro-4bora-3a,4a-diaza-s-indacene core. Most dyes in this class have many ideal characteristics for
PDT agents (low dark toxicities, cellular uptake, high extinction coefficients, low quantum
yields for photobleaching) hence modifications are possible that enable absorbance at long
wavelengths. However, most BODIPY dyes are efficiently excited into higher level singlet
states, fluoresce from these, and do not cross to triplets; in fact, observation of triplet excited
states in BODIPY dyes can be regarded as a novelty.47, 48 Photo-damage in PDT is thought
to occur predominantly via triplet excited states, consequently BODIPY dyes for PDT tend
to be modified to enhance intersystem crossing (ISC). Spin-coupling to heavy atoms is the
most common of these modifications (the “heavy atom effect”), and the one most frequently
encountered is halogenation. Appropriate placing of heavy atoms on the BODIPY core
promotes spin-orbit coupling, hence ISC, but not energy loss from excited states. Heavy
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atoms are not typically added to positions that could disrupt the planarity of the dye as this
would decrease conjugation.
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“Tetramethyl-BODIPY” 1 does not contain a halogen, or significantly populate triplet states
on excitation, and has a poor quantum yield (QY) for singlet oxygen (1O2) generation.
Nagano’s group was first to investigate a diiodo-analog, 2, for singlet oxygen generation in
PDT.40 Formation of 1O2 was inferred via a near IR absorbance at 1268 nm that emerged
when 2 was excited at 514 nm. Measurements of rate and QY for 1O2-generation in a
standard way, using 1,3-diphenylisobenzofuran (DBPF), revealed high efficiencies for this
process in both polar and apolar solvents. Unsurprisingly, then, compound 2 was shown to
have high light-to-dark photocytotoxicity ratios (HeLa cells). Nagano et al suggested high
oxidation potentials are desirable because they may protect BODIPY from self-oxidation.
They also argued that there are potential applications of PDT in membranes; apolar dyes like
2 are useful for studying effects in lipophilic media like this.
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Two studies have compared singlet oxygen generation of a range of iodinated BODIPYs. In
the first,41 iodination of meso-aryl substituents was found to have less impact than for coreattached iodines. However, simple incorporation of a meso-ethylene-carboxylic acid group
as in 3 improved the rate of singlet oxygen generation and light-induced photocytotoxicities
(two of three cell lines, the other was the same over 2). BODIPY 3 was found to localize in
the mitochondria of HSC-2 cells, and to induce G2/M arrest about 2 h after irradiation
caused apoptosis. In general the physical parameters for singlet oxygen generation in this
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series correlated with their light-induced photocytotoxicities; this is noteworthy because
such correlations are not always observed.
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The second study of iodinated BODIPYs involved compounds like 4 – 649 having iodine
atoms at different positions around the BODIPY core, and measurement of QYs of oxygen
generation for selected compounds. Surprisingly, introduction of iodines at the 3- and 5positions increases fluorescence. Flash photolysis experiments showed monoexponential
decay of the excited states of these dyes, consistent with predominant recovery to the
starting material state is indicative of high stability for photobleaching.
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Triplet excited states for BODIPY dyes are pertinent to triplet-triplet annihilation, hence
some groups have studied iodinated systems like the styryl-substituted one 7 and the dimers
8 – 9.50 Triplet lifetimes indicated for these structures were measured via time-resolved
spectroscopy. Estimates of triplet quantum QY were quoted based on 1 – (fluorescence QY),
but this is an overestimate because it assumes non-radiative decay processes are not
operative.
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A second study from Zhao and Li featured insertion of thiophene units between the iodine
and the BODIPY core. This gave dyes 10 and 11 that have exceptionally long triplet
lifetimes, slight red-shifted absorption and fluorescence maxima, and markedly decreased
extinction coefficients. These dyes also exhibit significant fluorescence indicating
incomplete ISC.51 Data specifically relating to the PDT properties of 7 – 11 has not been
reported.
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Thiophene is less aromatic than benzene, and its HOMO/LUMO energy levels are more
suitable for conjugation with some unsaturated fragments. Extended heterocycles containing
thiophene fragments can have similarly useful characteristics. For instance, in 12 and 13 the
heteroaryl-fused “KFL-4” BODIPY cores52, 53 have long wavelength absorption maxima,
high molar extinction coefficients, high QYs for 1O2 generation, and have higher
photostabilities than the clinically approved PDT agent (mTHPC). Moreover, these
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brominated compounds have residual fluorescence that might enable them to be used
simultaneously for imaging and PDT.
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Compound 7 above is an example of a “styryl-substituted” BODIPY. Akkaya’s group,
pioneers of this area, showed compounds like this are conveniently formed via Knoevenagel
reactions since 2,7-methyl substituents on BODIPYs are slightly acidic.54–57 In the first
contribution on the PDT characteristics of these compounds, Akkaya’s team made three
brominated systems that also have oligoethylene glycol fragments to promote watersolubilities.58 Compound 14 was the most studied of these; it had an EC50 (conc. required
for 50 % of the maximal effect; excitation at 625 nm) of 200 nM and the cytotoxicity was
attributed to cell-membrane damage as indicated via fluorescence microscopy.
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In a similar study, but featuring diiodo-BODIPY dyes, Ng and co-workers found 15 was the
most promising of four related potential PDT agents. They implied that this had the lowest
EC50 in the series (7 nM on HT29 carcinoma cells) possibly because it permeated into cells,
and accumulated inside, giving the most intense fluorescence. Fluorescence microscopy
experiments indicated this compound localized in the endoplasmic reticulum (ER, an
organelle involved in lipid and protein synthesis).
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The research on compound 15 described above was followed by more studies on styrylsubstituted BODIPYs, but this time ones with two different substituents. It was hypothesized
that the unsymmetrical substitution pattern would promote amphiphilic character.59 The
dimethylamine 16 was the most studied in this series; it had a low EC50 (17 nM) and
localized in lysosomes, less in mitochondria, and, unlike 15, not in the ER. Overall, the
authors concluded that the functional groups on the alkene were more important to the
localization behavior of the dyes than the lack of symmetry in the system. This paper is an
excellent reference for data on standards for singlet oxygen generation.6, 60
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An attractive feature of Akkaya’s route to styryl-substituted dyes is the diversity of aromatic
aldehydes that can be condensed to obtain these products. For instance, the pyrenecontaining systems 17 were prepared to facilitate non-covalent, supramolecular interactions
between these compounds and single-walled carbon nanotubes. Nanotubes of this kind are
internalized by mammalian cells, hence their interaction with the pyrene potentially could be
used for intracellular delivery of the PDT agent. Complexation of the nanotubes with the
agent was, in the event, observed and accompanied by a small decrease in the singlet oxygen
generation efficiency, but cytotoxicity studies have not been reported so far.
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Halogenated Aza-BODIPY PDT Agents
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Aza-BODIPYs like 1861, 62 have the BODIPY meso-carbon substituted by nitrogen, and this
has some surprising effects. Notably, aza-BODIPYs have absorbance and fluorescence
emissions of around 650 and 675 nm, and these may be displaced to even longer
wavelengths in compounds containing an electron donating group para-oriented relative to
the alkene (eg OMe in 18). Bromination of aza-BODIPY 2,6-positions results in at least a
four-fold reduction in fluorescence QY, and an increased population of triplet states upon
excitation giving at least 1000× differences between light and dark cytotoxicities. That parasubstituent also modulates PDT activity; for instance, the corresponding system without the
methoxide generated less singlet oxygen than 18, even when present at 100× the
concentration. Molar extinction coefficients of these systems are significantly better than
porphyrins. Unfortunately, the aqueous solubilities of aza-BODIPYs tend to be modest so
they are often delivered in cellular assays using cremophor (a common excipient used in
drugs to increase water solubilities, cf cremophor is used in formulations of paclitaxel for the
same reason).
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Compound 18 has a QY for singlet oxygen generation of 74 %.63 Time resolved
spectroscopy revealed its triplet quantum yield was 72% (lifetime 21 µs) and that the dye
was exceptionally photostable.63 The tetraiododibromo derivative 19 had a similar triplet
QY (78%; lifetime 1.6 µs).64 Quantum mechanical calculations (DFT) on these systems
have been used to understand their HOMO-LUMO levels and singlet-to-triplet energy
gaps.65
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Dibromo-aza-BODIPY 18 (designated as ADPM06 in papers) has been extensively studied
in cells and in vivo assays. It has a nanomolar EC50 for light-induced cytotoxicity in a range
of different human tumour cell lines, with no discernable selectivity for any particular type.
Encouragingly, these cell types include some drug-resistant and metastatic lines. Cells can
die via necrotic or apoptotic pathways; 18 administered at EC50 concentrations caused
apoptotic cell death. Moreover, even though cell death in PDT can be reduced under
depleted oxygen levels (eg hypoxia in cancer cells), 18 retained significant activity under
these conditions.60 Apoptosis is initiated in PDT mediated by 18 as a result of active oxygen
species generated around the ER. This is accompanied by activation of several inhibitor and
executioner caspases. Positron emission tomography studies using 18F-labeled agents
showed that a marked decrease in tumor proliferation (breast and glioma models) occurred
24 h past-PDT treatment with 18.60 In fact, ablation of breast tumors was observed in 71%
of mice treated with 18 at 2 mg Kg−1 after irradiation; this is comparable to “cure-rates” for
more established PDT agents in mice xenograft models. The inherent fluorescence of 18
facilitated studies to determine the organ distribution and clearance of this compound; the
data are consistent with that of an ideal initiator of PDT. There was no accumulation of 18 in
the skin, an important property for PDT agents. Positron emission tomography and magnetic
imaging studies showed that this PDT agent caused a decrease in tumour-vasculature
perfusion and -metabolic activity.66
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Applications of PDT are not limited to chemotherapy of cancer; another, though rarer, use of
these agents is as anti-bacterials. O’Shea and co-workers hypothesized that the quaternary
ammonium salt 20 may implant into bacterial membranes as a result of its positive charge
and amphiphilic character. Fluorescence studies with the non-halogenated analog 20
demonstrated this stains both gram-negative (E. coli) and -positive (S. aureus) bacteria, and
yeast cells (C. albicans) with a bias to the membrane regions. Encouragingly, a human cell
line (MDA-MB-231) showed only minimal uptake in the same timeframe. Strong
antibacterial activity on these microbes was observed when they were irradiated with 21;
total eradication occurred at concentrations of 1 – 5 µg mL−1.
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PDT Characteristics Modulated By Photoinduced Electron Transfer (PET)
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Several groups converged on the idea that photoinduced electron transfer (PET;
unfortunately, this is also a widely used abbreviation for positron emission tomography) can
be used to selectively quench intersystem crossing to triplet states. They have applied this
hypothesis in several different and ingenious ways.
Some PDT side-effects may arise from prolonged light sensitivity. O’Shea recognized that
aza-BODIPY dyes with a non-conjugated but proximal amine may undergo rapid relaxation
via PET processes when the amine is not protonated. However, a larger portion of the amine
would be protonated in the relatively acidic (pH 6.5 – 6.8) interstitial fluid that surrounds
tumours, PET would selectively diminish in those regions, and the cytotoxic effect would be
greater around cancerous cells than healthy ones.67 Dye 22 was the pivotal one used to
investigate this hypothesis. This agent was shown to generate more singlet oxygen in acidic
than in neutral media, and an EC50 value of 5.8 nM was recorded for light-induced
cytoxicity. However, to the best of our knowledge, photocytotoxicities of this agent in vivo
have not yet been compared with closely related compounds that lack the amine groups, so
the clinical potential of 22 is still an open question.
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Another way to use PET modulation of singlet-to-triplet conversion is via an appropriately
situated crown ether.68 Intracellular sodium ion concentrations are apparently around 3×
higher in tumor cells than in healthy ones, so coordination of these to a crown might
selectively increase the PET effect in tumour cells. Thus Akkaya and co-workers combined
meso-crown ether with pyridyl-styryl substituents in molecule 23 to sense higher sodium ion
and proton concentrations in tumour cells, respectively. The authors observed cumulative
effects of both stimuli in singlet oxygen generation, but conceded that the concentrations
required to achieve a desirable response were greater than intracellular levels; no cell studies
were reported.69
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An insightful assertion by Nagano et al was mentioned earlier in this review: that electron
withdrawing BODIPY-substituents should protect BODIPYs from oxidation. A recent study
from that group featured a range of BODIPY dyes with different electron withdrawing
groups in the 2- and 6-positions.70 Observation of singlet oxygen production confirmed
these dyes are most stable with electron withdrawing groups. A rough inverse correlation
between levels of singlet oxygen production and the electron withdrawing abilities of these
substituents was also noted. Observed QYs for singlet oxygen generation were probably not
high on an absolute scale (the paper did not mention what they were) but the study does
point to a fundamental issue: singlet oxygen generation can be modulated by tuning the
oxidation potential of the BODIPY core. This concept was used very effectively in the next
study from the Nagano lab, described below.
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All the applications of PDT so far target cells as a whole, wherein the mechanisms by which
the cell biology is disrupted are not of primary importance.71 On a molecular scale,
however, it is possible to use highly localized singlet oxygen generation to disable specific
proteins; this is the technique of chromophore assisted light inactivation (CALI). Nagano’s
group had the idea that a hydrophobic BODIPY-based sensitizer might bury itself in a
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lipophilic cavity of a protein receptor when brought into proximity via binding to a
conjugated ligand. This strategy is likely to be most effective when singlet oxygen
production is enhanced by placing the sensitizer in a lipophilic environment. The specific
case studied was inositol 1,4,5-trisphosphate (IP3) coupled to a 2,6-diiodo-BODIPY; the
hypothesis was that ligand binding would place the dye into a hydrophobic cavity that is
easily seen in the receptor that binds IP3 (IP3R). They showed the electron donating
substituent in structures 25 modulated the properties of the sensitizer such that the
production of singlet oxygen was slow except in relatively apolar solvents.
An attribute of this particular system is that binding to IP3R gives a measurable biochemical
output, ie increased Ca2+ concentration. Thus binding of the 2,6-diiodo-BODIPY conjugate
gave dose-dependent release of Ca2+ with an EC50 value of 3 µM, while 2,6-diiodoBODIPY conjugated with the enantiomeric IP3-ligand did not give the same Ca2+ release.
Permeablized cells were then used to input a calcium ion sensor and the appropriate
conjugates; only the ones with an environment-activated photosensitizer conjugated to the
appropriate IP3-ligand enantiomer gave calcium release that was negatively modulated by
treatment with light (Figure 1).
Halogen-free BODIPY Sensitizers
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There is nothing special about halogen atoms in design of BODIPY derivatives for tripletsensitization; any substituent with molecular orbitals having appropriate multiplicity and
energy levels might function in this way. Surprisingly, some BODIPY fragments have
emerged as appropriate substituents to induce triplet-sensitization. Thus, dimers of BODIPY
dyes wherein the chromophores are directly connected may, on excitation, undergo more
efficient ISC to triplet states than the corresponding monomers.72
Computational studies have been used to predict orthogonal chromophores that may give
electronic mixing in the excited states to generate triplets. Selection of the appropriate
computational method is important; here multiconfigurational self-consistent field, MCSFF,
was used. Just as predicted, bisBODIPY systems like 26 were less fluorescent than their
constituent monomers, and gave relatively high singlet QYs. An EC50 of 50 nM was
measured for human erythroleukemia cells.73
Attempts to extend conjugation using the styryl approach failed to give triplet oxygen
production at higher wavelengths. We suggest this could be due to accelerated
photobleaching of a long-lived triplet excited state.74
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BODIPY derivative 27 is an organic triplet photosensitizer; it is particularly interesting
because no halogens or other heavier elements are involved.75 It appears that the BODIPY
fluorescence is quenched via intramolecular energy transfer to the styryl protected C60dyads, accounting for the long-lived triplet excited state (123.2 µs) of this material.
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BODIPY Dyes For Observing Reactive Oxygen Species
There are BODIPY-derivatives designed to be sensors for the generation of reactive oxygen
species. These are not necessarily PDT agents, but they can be used to monitor
consequences of PDT treatment. One useful probe of this kind is the commercially available
C11-BODIPY. For example, this probe was used to demonstrate that oxidants were present
in a cell culture up to 30 min after illumination on a PDT experiment. A dark control
showed hydrogen peroxide only activated the probe when it was in direct contact with the
cells so the researchers were able to deduce that the reactive oxygen species involved in the
PDT experiment were not confined to peroxide anions.76
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Conclusions
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Many studies have focused on BODIPY core modifications to facilitate singlet oxygen
generation. The intrinsic absorption maxima of simple BODIPY dyes (ca 510 – 530 nm) is
shorter than ideal, so many of the featured modifications also aim to extend conjugation in
these molecules. For instance, Akkaya’s methyl-BODIPY condensation reaction has been
used several times, including studies by other groups, for this purpose. One of the most
promising avenues of research, pioneered mainly by O’Shea, centers on aza-BODIPY
compounds as PDT agents; these are less synthetically accessible, but have red-shifted
absorption maxima. In our view, aza-BODIPY agents are probably closer to clinical
development than any subcategory in the BODIPY class.
An interesting consequence of the PDT work is Nagano’s CALI technique to eliminate
selected receptors on a molecular level. This approach is mostly intended for in vitro and
cellular studies, so wavelength of absorption is not critical. BODIPY dyes can also be used
as sensors for reactive oxygen species in studies involving other types of agents.
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A priority for future research must be to develop clinically useful PDT agents. Possibly this
will be coupled with active-targeting. Thus it will be interesting to see future studies
featuring BODIPYs conjugated with ligands for cell-surface receptors that are overexpressed on tumour cells. It is surprising that we did not encounter reports of this strategy,
even employing common small molecule targeting agents like RGD peptidomimetics and
folic acid.
Acknowledgments
We thank The National Institutes of Health (GM087981), The Robert A. Welch Foundation (A-1121), and HIRMOHE grant (UM.C/625/1/HIR/MOHE/MED/17), Ministry of Higher Education, Malaysia for financial support.
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Figure 1.
Binding of a functionalized BODIPY to the inositol 1,4,5-trisphosphate receptor places the
PDT agent in a hydrophobic environment where singlet oxygen generation is favored,
leading to inactivation of the protein.
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Figure 2.
Excitation of bisBODIPY systems like 26 gives singlet excited states (blue electrons), but a
triplet state (red) is also favored.
Chem Soc Rev. Author manuscript; available in PMC 2014 January 07.
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3 00013
5 00013
63013
63513
650
(EtOH)19
652
(H2O)19
688 (PBS
+2%
TX100)23
692
(PBS)23
654
(PBS)25
663
(PBS)27
Porfimer
sodium
(Photofrin®)
Protoporphyrin
IX
(Levulan®)
Temoporfin
(Foscan®)
Verteporfin
(Visudyne®)
Talaporfin
(Laserphyrin®)
Ce6
(Photolon®)
Chem Soc Rev. Author manuscript; available in PMC 2014 January 07.
662
(PBS)27
660
(PBS)25
694 (PBS
+2%
TX100)23
695
(PBS)23
655
(PBS)20
630 (ex
397 nm;
PBS)17
NA
λmax emiss
(nm)
0.18
(PBS)27
NA
0.049 (PBS
+2%
TX100)23
0.002
(PBS)23
NA
0.011 (ex
397 nm;
PBS)17
NA
ΦFl
0.82
(PB + 1 % TX100;
692 nm; lysozyme
inactivation; MB at
0.52)18
0.77
(D2O, oxygen
depletion with
FFA)25
5.35 × 10−5
(PBS + 2 %
TX100)23
2.80 × 10−5
(PBS)23
8.2 × 10−4
(PBS)25
0.75
(PB; 660 nm;
lysozyme
inactivation; MB at
0.52)18
0.31
(PBS + 10 %
FCS; >610 nm;
DPBF; hypericin
at 0.36)21
1.54 × 10−5
(PBS + 10
% FCS)21
NA
0.54
(PB + 1 % TX100;
630 nm; lysozyme
inactivation; RB at
0.75)18
0.25 (PB + 1 %
TX100; 630 nm;
oxygen depletion
with FFA)15
ΦΔ
NA
5.4 × 10−5
(PB)14
ΦPB
Log Po/w
0.7827
−1.9226
7.76 (calc.)24
9.2422
NA
X100; FFA – furfuryl alcohol; MB – methylene blue; RB – rose Bengal; NA – not available
yield; ΦΔ - singlet oxygen generation quantum yield; Log Po/w – log octanol/water partition coefficient; PB – phosphate buffer pH~7.4; EtOH – ethanol; PBS – phosphate buffered saline; TX100 – Triton
Abbreviation: λmax abs - absorption maxima (Q-band); ε - molar extinction coefficient; λmax emiss - fluorescence emission maxima; ΦFl - fluorescence quantum yield; ΦPB - photobleaching quantum
38 000
(PBS)27
40 000
(PBS)25
31 200
(PBS + 2 %
TX100)23
13 500
(PBS)23
39 000
(EtOH)19
23 000
(H2O)19
ε (M−1 cm−1)
λmax abs
(nm)
Photosensitizer
3.96 (calc.)16
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Spectroscopic and physicochemical properties of clinical approved photosensitizers
NIH-PA Author Manuscript
Table 1
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