Abstract
Radiotherapy is an important therapeutic strategy for cancer treatment through direct damage to cancer cells and augmentation of antitumor immune responses. However, the efficacy of radiotherapy is limited by hypoxia-mediated radioresistance and immunosuppression in tumor microenvironment. Here, we construct a stabilized theranostic nanoprobe based on quantum dots emitting in the near-infrared IIb (NIR-IIb, 1,500–1,700 nm) window modified by catalase, arginine–glycine–aspartate peptides and poly(ethylene glycol). We demonstrate that the nanoprobes effectively aggregate in the tumor site to locate the tumor region, thereby realizing precision radiotherapy with few side-effects. In addition, nanoprobes relieve intratumoral hypoxia and reduce the tumor infiltration of immunosuppressive cells. Moreover, the nanoprobes promote the immunogenic cell death of cancer cells to trigger the activation of dendritic cells and enhance T cell-mediated antitumor immunity to inhibit tumor metastasis. Collectively, the nanoprobe-mediated immunogenic radiotherapy can boost the abscopal effect to inhibit tumor metastasis and prolong survival.
Highlights
Radiotherapy is an important therapeutic strategy for cancer treatment through direct damage to cancer cells and augmentation of antitumor immune responses
8-Arm poly(ethylene glycol) (PEG)-NH2 molecules, RGD peptides, and Cat were conjugated on the surface of Oleyamine-branched poly(acrylic acid) (OPA)-modified Quantum dots (QDs) via N-(3-(dimethylamino)propyl)-N′ethylcarbodiimide hydrochloride (EDC) chemistry[32]
The results showed that tumor tissue significantly increased the surface expression of calreticulin and adenosine triphosphate (ATP) and high-mobility group box 1 (HMGB1) concentrations (Supplementary Fig. 7a–c) at 24 h after the mice treated with QD-RGD- or QD-Cat-RGDbased RT, which was consistent with the in vitro results
Summary
Radiotherapy is an important therapeutic strategy for cancer treatment through direct damage to cancer cells and augmentation of antitumor immune responses. The nanoprobes promote the immunogenic cell death of cancer cells to trigger the activation of dendritic cells and enhance T cell-mediated antitumor immunity to inhibit tumor metastasis. One common hypothesis is that localized RT initiates immunogenic cell death (ICD) of cancer cells and induces presentation by dendritic cells (DCs), leading to prime antitumor immunity mediated by tumor-specific cytotoxic T cells[9,10]. Localized RT enriches the cytotoxic T cell infiltrate in tumor tissue resulting in regression of the primary tumor and produces systemic tumor-directed immunity, leading to elimination of metastatic cancer in the non-irradiated field (called the abscopal effect) and long-term immunological memory, especially when combined with immunotherapy[11,12]. Relieving the hypoxic environment in the TME can effectively improve the RT-induced antitumor immune response and abscopal effect
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