Triangle-Shaped Tellurium Nanostars Potentiate Radiotherapy by Boosting Checkpoint Blockade Immunotherapy

• Published in: Matter Vol. 3; no. 5; pp. 1725 - 1753
• Main Authors: Huang, Wei, He, Lizhen, Ouyang, Jiang, Chen, Qi, Liu, Chuang, Tao, Wei, Chen, Tianfeng
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 04.11.2020
• Subjects: immunotherapy; radiosensitization; tellurium; triangle nanostars; tellurium; MAP5: Improvement; triangle nanostars; radiosensitization; immunotherapy
• ISSN: 2590-2385; 2590-2385
• DOI: 10.1016/j.matt.2020.08.027

Checkpoint blocking-based immunotherapy has been proved to be effective for the treatment of cancer, but its dependence on T cell infiltration has limited its effectiveness across patients. Radiotherapy (RT) is becoming the most common method of clinical tumor treatment but can occasionally cause systemic tumor rejection. Here, we demonstrate a simple one-pot hydrothermal method to synthesize tellurium (Te) nanostars (GTe-RGD) and offer a treatment strategy that combines GTe-RGD-potentiated RT with checkpoint blockade immunotherapy for efficient and systemic tumor elimination. In mouse models of breast cancer, GTe-RGD-potentiated RT not only eradicated primary tumors but also elicited antitumor immunity to inhibit growth at distant sites by enhancing cytotoxic T lymphocytes when combined with an immune checkpoint inhibitor. Furthermore, the triggered release of tumor-associated antigens and cytokines can effectively reduce the percentage of M2 macrophages with enhanced antitumor activity. Thus, this simply synthesized Te-based nanomedicine, with radiation-driven immunotherapy, offers an attractive clinical alternative for tumor treatment. [Display omitted] •Triangle-shaped Te nanostars were fabricated via one-pot hydrothermal method•GTe-RGD possesses excellent radiosensitization activity•GTe-RGD combines with radiotherapy/anti-PD-1 to boost immunotherapy Radiotherapy (RT) triggered by high-energy radiation is becoming one of the most effective tools for clinical treatment of malignant tumor via an indirect reaction with water to generate reactive oxygen species or causing DNA damage to induce cancer cell apoptosis. However, therapeutic outcomes of RT are plagued by radiation resistance among tumor cells and toxic side effects on normal tissues. Checkpoint blocking-based immunotherapy has been proved to be effective for the treatment of cancer, but its dependence on T cell infiltration has limited its effectiveness across patients. Therefore, to overcome this bottleneck, we not only provide a simple way to synthesize triangle-shaped nanostars but also provide a valid approach to efficient and successful tumor elimination by combining RT with immunotherapy, which makes it possible to trigger systemic immune responses after local treatment and offers great potential for future clinical translation. This study provides a facile way to synthesize triangle-shaped Te nanostars and an effective cancer treatment strategy by combination of radiotherapy and immunotherapy, which makes it possible to activate systemic immune responses after local treatment, with great potential for clinical translation.