A systematic review on the development of radiosensitizers, with cancer selectivity, for radiotherapy using ionizing radiation

Background: At present, radiotherapy (RT) is widely used in cancer treatment, but traditional RT methods using ionizing radiation cannot avoid damage to normal tissues. Therefore, the development of a more precise RT is an important research direction for relevant researchers. Concurrently, research on radiosensitizers (RSs) using nanotechnology is developing rapidly, and RSs that are selective for cancerous tissues or cancer cells may become an important part of future precision RT. Methods: Using RSs and RT as keywords, the relevant papers in the PubMed database from 2013 to 2022 were summarized. Articles on RS with selectivity to cancer tissue were collected. Among the selected articles, RSs were classified into "active selectivity", "passive selectivity" and "others" according to the different selectivity principles of RSs. Results: A total of 771 articles were retrieved from PubMed. After screening, the research content of the remaining 79 articles was found to be related to the selectivity of RSs to cancer tissues. Among them, 28 articles were classified as "active selectivity", and most of the sensitizers in this category could target specific targets in cancer tissues. There were 30 papers classified as "passive selectivity" and the selectivity principles were mainly the enhanced permeability and retention (EPR) effect, aggregation caused by pH sensitivity, and aggregation in anoxic environments. There were 21 papers classified as "others". The sensitizers in these studies showed selectivity for cancer tissue, but the mechanism was not clear. This review attempts to summarize studies on RSs that are selective for cancer tissues. Conclusions: We reviewed nearly ten years of literature on selective RSs and classified the selectivity of different RSs into active and passive selectivities.