Cancer Treatment with Built-in Light
Therapies should be highly effective and as free as possible of side effects -- a big challenge, particularly with cancer. A Chinese research team has now developed a novel form of photodynamic tumour therapy to treat deep tumours that works without external irradiation. They built the light source into the drug and is "switched on" selectively in the microenvironment of tumours, 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. They administered a photosensitizer, then they irradiate the region where the tumour is located with light. The light excites the photosensitizer and transfers some absorbed energy to oxygen molecules, resulting in reactive oxygen species that destroy tumour cells. Because of the limited depth of penetration of the visible or UV light in tissues, this method is only useful for shallow tumours.
A team led by Xiaolian Sun (China Pharmaceutical University, Nanjing) and Guoqiang Shao (Nanjing Medical University) has now developed a new photodynamic tumour therapy that works for deep tumours. 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 tumour.
This "intelligent" drug comprises 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 tumour 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 polarise atoms, 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. Here, the quenching of the waves is incomplete, resulting in a bluish light known as Cherenkov radiation. This excites the photosensitizers enough to destroy tumour cells. In cell cultures and animal models, the new drug showed powerful tumour inhibition with low toxicity and minimal side effects on healthy tissue.
Jingru Guo, Kai Feng, Wenyu Wu, Yiling Ruan, Huihui Liu, Xiuping Han, Guoqiang Shao, Xiaolian Sun. Smart 131 I?Labeled Self?Illuminating Photosensitizers for Deep Tumor Therapy. Angewandte Chemie International Edition, 2021; DOI: 10.1002/anie.202107231
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