Tailoring bismuth-based nanoparticles for enhanced radiosensitivity in cancer therapy

Achieving a complete response to cancer treatment is a severe challenge, and has puzzled humans for a long time. Fortunately, radiotherapy (RT) gives rise to a common clinical treatment method, during which the usage of radiosensitizers is essential. Among preclinical radiosensitizers, bismuth-based nanoparticles (Bi-based NPs) are widely explored in cancer diagnosis and treatment, because they share favourable properties, such as low toxicity, strong X-ray absorption and facile preparation. However, pure Bi alone cannot achieve both efficient and safe RT outcomes, mainly due to poor targeting of tumor sites, long retention-induced systemic toxicity and immune resistance. This work provides an overview of recent advances and developments in Bi-based NPs that are tailored to enhance radiosensitivity. For the fabrication process, surface modification of Bi-based NPs is essential to achieve tumor-targeted delivery and penetration. Moreover, the incorporation of other elements, such as Fe ions, can increase diagnostic accuracy with optimal theranostic efficacy. Meanwhile, the structure-activity relationship can also be manipulated to maximize the chemotherapeutic drug loading capability of Bi-based NPs, to enhance X-ray attenuation by means of a large surface area or to achieve safer metabolic routes with rapid clearance from the human body. In addition, Bi-based NPs exhibit synergistic antitumor potential when combined with diverse therapies, such as photothermal therapy (PTT) and high-intensity focused ultrasound (HIFU). To summarize, the latest research on Bi-based NPs as radiosensitizers is described in the review, including both their advantages and disadvantages for improving treatment, thus providing a useful guide for future clinical application.