In situ radiotherapy for gastric cancer: The role of gold and other inorganic nanoparticles.

The use of X-rays as a first-line treatment for gastric tumors is constrained by inaccurate target delineation and high toxicity to surrounding healthy tissues. The potential of inorganic nanoparticles (INPs; e.g. gold, silver, titanium oxide, tungsten oxide) in imaging and cancer therapy has been discussed as a solution to improve radiotherapy effectiveness, particularly in situations of challenging organ segmentation. X-rays interact with these INPs leading to the release of photons and electrons motivated by the photoelectric effect and Compton scattering that induces a cascade effect, resulting in the breakdown of DNA strands of tumor cells. Despite the associated radio-enhancing advantages, concerns have been raised regarding the bioaccumulation and potential toxicity of these nanoparticles, which could limit their administration and, consequently, their efficiency. To address these limitations, delivery systems based on novel biomaterials designs have been developed. These systems aim of achieve a more localized effect of NPs through targeting strategies, functionalization and use of delivery platforms that do not compromise surrounding healthy tissues. This review discusses the results of dose escalation induced by INPs in gastric tumors, along with the impact of design of INPs on the radiobiological effects observed. Furthermore, it explores prospective developments for combined therapy and potential alternatives for local delivery of nanoparticles. STATEMENT OF SIGNIFICANCE: Gastric cancer (GC) affects over more than one million globally each year. Considering the limited efficacy of chemo- and radiotherapies, surgical resection remains the standard treatment. However, stomach function and the patient quality of life are often compromised after surgical intervention. To enhance the effectiveness of radiotherapy in GC, small particles - typically composed of high atomic number materials - are being explored for their ability to increase tumor cell sensitivity to the X-rays. The delivery strategies and optimal design of these particles within the gastric environment are critical factors under investigation to maximize their radiosensitizing effects. The reduction of treatment invasiveness, and gastric cancer recurrence are key aspects associated with the translation of this approach to clinical routine.