AI Article Synopsis
- Radiotherapy can enhance cancer treatment by reducing chemotherapy's harmful side effects, but current radiation-activated protecting groups are limited.
- Researchers introduced N-alkyl-4-picolinium (NAP) as a promising new radiation-responsive caging group that effectively releases client molecules when exposed to radiation.
- The study demonstrated that ADCs using NAP-derived linkers can efficiently release active compounds in cells and mice, suggesting they could lead to more effective and stable cancer therapies in the future.
Article Abstract
Radiotherapy-induced prodrug activation provides an ideal solution to reduce the systemic toxicity of chemotherapy in cancer therapy, but the scope of the radiation-activated protecting groups is limited. Here we present that the well-established photoinduced electron transfer chemistry may pave the way for developing versatile radiation-removable protecting groups. Using a functional reporter assay, N-alkyl-4-picolinium (NAP) was identified as a caging group that efficiently responds to radiation by releasing a client molecule. When evaluated in a competition experiment, the NAP moiety is more efficient than other radiation-removable protecting groups discovered so far. Leveraging this property, we developed a NAP-derived carbamate linker that releases fluorophores and toxins on radiation, which we incorporated into antibody-drug conjugates (ADCs). These designed ADCs were active in living cells and tumour-bearing mice, highlighting the potential to use such a radiation-removable protecting group for the development of next-generation ADCs with improved stability and therapeutic effects.
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| http://dx.doi.org/10.1038/s41557-024-01501-4 | DOI Listing |
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