Abstract
Hypoxic tumor cell sub-populations are highly resistant to radiotherapy and their presence frequently causes disease recurrence and death. Here, we described the physicochemical properties required to develop superior tumor-targeted hypoxia-activated modular prodrugs that liberate extremely short-lived bis(sulfonyl)hydrazines (BSHs) as reactive cytotoxins, thereby precisely focusing cytotoxic stress on these radio-resistant hypoxic sub-populations. Therefore, cytotoxic stress will be focused on radiation resistant areas and thus strongly synergizing with radiotherapy.