Deep photodynamic therapy: photosensitizer irradiates itself
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Therapies should be highly effective and as free as possible of side
effects—a big challenge, particularly in the case of cancer. A Chinese
research team has now developed a novel form of photodynamic tumor
therapy for the treatment of deep tumors that works without external
irradiation. The light source is built into the drug and is “switched
on” selectively in the microenvironment of tumors, as they report in the
journal Angewandte Chemie.
Classic photodynamic therapy is a noninvasive cancer treatment that
is relatively gentle because of its specific spatial and temporal
selectivity. To start with, a photosensitizer is administered, then the
region where the tumor is located is irradiated with light. The
photosensitizer is excited by the light and transfers some of the
absorbed energy to oxygen molecules, resulting in reactive oxygen
species that destroy tumor cells. Because of the limited depth of
penetration of the necessary visible or UV light in tissues, this method
is only useful for shallow tumors.
A team led by Xiaolian Sun (China Pharmaceutical University, Nanjing)
and Guoqiang Shao (Nanjing Medical University) has now developed a new
photodynamic tumor therapy that works for deep tumors. It does not need
external irradiation because the photosensitizer brings its own “lamp”
along and “switches it on” on its own once it reaches the tumor.
This “intelligent” drug consists of four components linked into a single molecule: a photosensitizer (pyropheophorbide-a),
a pH sensor (diisopropylamino group), a polymer (polyethylene glycol),
and the “lamp” (the amino acid tyrosine carrying a radioactive
iodine-131 isotope). At the pH values found in healthy tissues, the
molecules are tightly aggregated into nanoparticles. In this compact
form, the “irradiation” is switched off (quenched) and the drug has no
effect. However, tumorous tissue has a somewhat more acidic pH value.
This environment causes the pH sensor to change structure, and the
nanoparticles fall apart—the irradiation is switched on, and reactive
oxygen species are formed that kill the tumor cells.
How does this “built-in light” work? As it decays, the radioactive
iodine isotope I-131 releases β-radiation (electrons) and γ-radiation.
As the electrons move, their charges polarize atoms, thereby causing
dipole oscillations that send out electromagnetic waves, which means
light. Usually, these waves cancel one another immediately. Yet, in the
dense aqueous environment of the cells (other than in vacuo), the
electrons sent out by I-131 are faster than light. In this case, the
quenching of the waves is incomplete, resulting in a bluish light known
as Cherenkov radiation. This excites the photosensitizers enough to
destroy tumor cells. In cell cultures and animal models, the new drug
demonstrated powerful tumor inhibition with low toxicity and minimal
side effects on healthy tissue.
(2981 characters)
About the Author
Dr. Xiaolian Sun is a
Professor at China Pharmaceutical University with appointments in
Pharmaceutical Studies. Her main specialty is molecular imaging probe
development and nanomedicine for drug delivery.
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Permalink to the original article: https://doi.org/10.1002/anie.202107231
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