Radiotherapy is a key pillar of solid cancer treatment. Despite a high level of conformal dose deposition, radiotherapy is limited due to co-irradiation of organs at risk and subsequent normal tissue toxicities. Nanotechnology offers an attractive opportunity for increasing the efficacy and safety of cancer radiotherapy. Leveraging the freedom of design and the growing synthetic capabilities of the nanomaterial-community, a variety of engineered nanomaterials have been designed and investigated as radiosensitizers or radioenhancers. While research so far has been primarily focused on gold nanoparticles and other high atomic number materials to increase the absorption cross section of tumor tissue, recent studies are challenging the traditional concept of high-Z nanoparticle radioenhancers and highlight the importance of catalytic activity. This review provides a concise overview on the knowledge of nanoparticle radioenhancement mechanisms and their quantification. It critically discusses potential radioenhancer candidate materials and general design criteria for different radiation therapy modalities, and concludes with research priorities in order to advance the development of nanomaterials, to enhance the efficacy of radiotherapy and to increase at the same time the therapeutic window.

Nanoparticle-based radioenhancement is a promising strategy for extending the therapeutic ratio of radiotherapy. While (pre)clinical results are encouraging, sound mechanistic understanding of nanoparticle radioenhancement, especially the effects of nanomaterial selection and irradiation conditions, has yet to be achieved. Here, we investigate the radioenhancement mechanisms of selected metal oxide nanomaterials (including SiO₂, TiO₂, WO₃and HfO₂), TiN and Au nanoparticles for radiotherapy utilizing photons (150 kVp and 6 MV) and 100 MeV protons. While Au nanoparticles show outstanding radioenhancement properties in kV irradiation settings, where the photoelectric effect is dominant, these properties are attenuated to baseline levels for clinically more relevant irradiation with MV photons and protons. In contrast, HfO₂nanoparticles retain some of their radioenhancement properties in MV photon and proton therapies. Interestingly, TiO₂nanoparticles, which have a comparatively low effective atomic number, show significant radioenhancement efficacies in all three irradiation settings, which can be attributed to the strong radiocatalytic activity of TiO₂, leading to the formation of hydroxyl radicals, and nuclear interactions with protons. Taken together, our data enable the extraction of general design criteria for nanoparticle radioenhancers for different treatment modalities, paving the way to performance-optimized nanotherapeutics for precision radiotherapy.

Millions of patients every year undergo gastrointestinal surgery. While often lifesaving, sutured and stapled reconnections leak in around 10% of cases. Currently, surgeons rely on the monitoring of surrogate markers and clinical symptoms, which often lack sensitivity and specificity, hence only offering late-stage detection of fully developed leaks. Here, we present a holistic solution in the form of a modular, intelligent suture support sealant patch capable of containing and detecting leaks early. The pH and/or enzyme-responsive triggerable sensing elements can be read out by point-of-need ultrasound imaging. We demonstrate reliable detection of the breaching of sutures, in as little as 3 hours in intestinal leak scenarios and 15 minutes in gastric leak conditions. This technology paves the way for next-generation suture support materials that seal and offer disambiguation in cases of anastomotic leaks based on point-of-need monitoring, without reliance on complex electronics or bulky (bio)electronic implantables.

Despite decades of research, wound complications remain a major cause of postoperative mortality, especially in the face of multiple comorbidities. Addressing the issue of anastomotic leakages and impaired wound healing from a new angle is of great interest with the prospect of having direct impact on patient outcome. Recently, aqueous suspensions of silica and iron oxide nanoparticles have been employed to connect biological tissue by serving as an adhesive layer eventually leading to macroscopic gluing of tissue. In this work, we explore the prospects of this effect by introducing bioactive tissue adhesives composed of nanoparticles produced via scalable and sterile flame spray pyrolysis. We investigate six different metal oxides on cytocompatibility, hemostatic activity and adhesive properties in a small intestine lap joint model. While bioglass nanoparticles show exceptionally strong procoagulant and adhesive properties, the cell membrane integrity is impaired at high particle concentrations. Interestingly, when bioglass is combined with ceria, a material that has well-documented cytoprotective effects, the resulting hybrid particles exhibit the same beneficiary effects as bioglass while featuring superior cytocompatibility. Taken together, we demonstrate highly modular synthesis of nanoparticles expressing adhesive properties in conjunction with tailored bioactivity. Such bioactive nanoparticles as adhesion nuclei in wound healing have a wide range of potential applications in surgical wound care and regenerative medicine.