Near-Infrared Light-Responsive Nitric Oxide Delivery Platform for Enhanced Radioimmunotherapy

Abstract

HIGHLIGHTS • Ag 2 S NO delivery platforms maximize radiotherapy effects remarkably to inhibit the tumor growth. • Immunosuppressive tumor microenvironment was improved by Ag 2 S NO delivery system, significantly enhancing the anti-PD-L1 immune checkpoint blockade therapy. ABSTRACT Radiotherapy (RT) is a widely used way for cancer treatment. However, the efficiency of RT may come with various challenges such as low specificity, limitation by resistance, high dose and so on. Nitric oxide (NO) is known a very effective radiosensitizer of hypoxic tumor. However, NO cannot circulate in body with high concentration. Herein, an NIR light-responsive NO delivery system is developed for controlled and precisely release of NO to hypoxic tumors during radiotherapy. Tert-Butyl nitrite, which is an efficient NO source, is coupled to Ag 2 S quantum dots (QDs). NO could be generated and released from the Ag 2 S QDs effectively under the NIR irradiation due to the thermal effect. In addition, Ag is also a type of heavy metal that can benefit the RT therapy. We demonstrate that Ag 2 S NO delivery platforms remarkably maximize radiotherapy effects to inhibit tumor growth in CT26 tumor model. Furthermore, immunosuppressive tumor microenvironment is improved by our NO delivery system, significantly enhancing the anti-PD-L1 immune checkpoint blockade therapy. 100% survival rate is achieved by the radio-immune combined therapy strategy based on the Ag 2 S NO delivery platforms. Our results suggest the promise of Ag 2 S NO delivery platforms for multifunctional cancer radioimmunotherapy.

Photoactivatable nanogenerators of reactive species for cancer therapy

“…However, NO-based combination therapy has been extensively studied. Current ● NO-based treatment research mainly focuses on four pathways, including high concentration-induced cytotoxicity [ 127 ], as a chemotherapy sensitizer [ 128 ], as radiation therapy sensitizer [ 129 ], or as phototherapy sensitizer [ 120 , 122 ]. The ever-increasing antitumor research about the combination of ● NO therapy with various therapeutic strategies demonstrated the great significance of summarizing the related research works.…”

“…(c) The preparation of Ag 2 S@BSA-SNO for cancer therapy. Reprinted with permission [ 129 ]. Copyright 2020, Springer Nature.…”

Combined Application of Nanotechnology and Multiple Therapies with Tumor Immune Checkpoints

“…In recent years, photodynamic therapy “PDT” and photothermal therapy “PTT” and other phototherapy techniques have been increasingly studied in tumor treatment [76] . The photosensitizer used in photodynamic therapy can convert the oxygen in the tumor into singlet oxygen or reactive oxygen species (ROS) [77] . PTT is a non‐invasive strategy that used near‐infrared light and photothermal conversion agents to increase the temperature of the tumor area [78] .…”

“…[76] The photosensitizer used in photodynamic therapy can convert the oxygen in the tumor into singlet oxygen or reactive oxygen species (ROS). [77] PTT is a non-invasive strategy that used near-infrared light and photothermal conversion agents to increase the temperature of the tumor area. [78] Both PDT and PTT can induce tumor vascular necrosis and cancer cell apoptosis.…”

A pH‐responsive polymer linked with immunomodulatory drugs: synthesis, characteristics and in vitro biocompatibility

“…For instance, the chemicals used in traditional chemotherapy are difficult to penetrate into tumor centers and are prone to develop drug resistance (W. Han et al, 2018; Xie, Wan, Chen, Han, & Wang, 2020; Q. Zhou et al, 2018). Radiation therapy and surgical treatment might induce serious adverse effects to normal cells/tissues and promote tumor metastasis (Chen et al, 2018; Shu et al, 2020; X. Zhou et al, 2020). Therefore, novel cancer therapies with higher therapeutic efficacy to cancer cells/tissues and lower toxicity to normal cells/tissues are still being developed.…”