NIR Responsive Injectable Nanocomposite Thermogel System Against Osteosarcoma Recurrence

Compared to traditional postoperative radiation and chemotherapy, immune checkpoint blockade (ICB) therapy demonstrates superiority by provoking own immune system to cure cancer completely even for some terminally ill patients. However, systemic administration of ICB is liable to cause severe immunity inflammation or immune storm. Here, an injectable, near infrared (NIR) responsive, multifunctional nanocomposite thermogel as a local ICB delivery system for cancer postsurgical therapy is proposed. By copolymerization of thermosensitive and zwitterionic monomer, the injectable thermogel with adjustable sol-gel transition temperature is obtained. Afterward, combined with functional mesoporous nanoparticles, the platform can absorb NIR light and transfer it into heat. The generated heat will promote retro Diels-Alder (D-A) reaction to degrade coating layer on nanoparticle, achieving NIR controlled ICB release. Furthermore, the local ICB delivery system is applied on an osteosarcoma postsurgical recurrence model and results indicate the platform with favorable biocompatibility can avoid early leakage of cargos and greatly increase drug content at tumor site. Besides, long-term controlled ICB release of the system effectively improves the amount of active T cells, resulting in excellent antitumor recurrence effect. Overall, this work suggests the local injectable nanocomposite thermogel is expected to be a promising tool for cancer postoperative therapy.