Due to the immunosuppressive tumor microenvironment (TME) and weak radiation absorption, the immune response triggered by radiation therapy (RT) is limited. Herein, a core–shell nanosensitizer UiO@MnS (denoted as UM) was genuinely constructed for the amplification of RT efficacy and induction of immunogenicity via integrating MnS-reprogrammed TME with Hf-based UiO-sensitized RT. The acid-sensitive MnS would produce H2S under acidic TME to improve oxygenation through inhibition mitochondrial respiration and reducing metabolic oxygen consumption, leading to decreased HIF-1α expression and enhanced radiosensitization. In addition, the generated H2S inhibited the catalase activity to increase the H2O2 level, which subsequently enhanced the Mn2+-mediated Fenton-like reaction, resulting in G2/M cell cycle arrest to improve the cellular sensitivity for radiation. This impressive tumor oxygenation, cell cycle arrest, and radiosensitization procedure boosted RT efficacy and resulted in strong antitumor immunogenicity. Taken together, combining the immunosuppressive TME modulation with a sensitizing radiation strategy shows great promise for magnifying immunogenic RT outputs.
Radiotherapy (RT) is a major treatment method for non-small-cell lung cancer (NSCLC), and development of new treatment modality is now critical to amplify the negative effects of RT on tumors. In this study, we demonstrated a nanoparticle-loaded block copolymer micellar system for cancer hyperthermia treatment (HT) that can be used for synergistic therapy under alternating magnetic field (AMF) and radiation field. Block copolymer micelles (polyethylene glycol-block-polycaprolactone, or PEG-PCL) containing hyaluronic acid (HA) and Mn–Zn ferrite magnetic nanoparticles (MZF) were fabricated via a two-step preparation. HA-modified Mn–Zn ferrite magnetic nanoparticles (MZF-HA) can be enriched in CD44 highly expressing tumor cells, such as A549 (human lung adenocarcinoma cell line), through an active targeting mechanism via receptor–ligand binding of HA and CD44 (HA receptor). MZF can generate thermal energy under an AMF, leading to a local temperature increase to approximately 43 °C at tumor sites for mild HT, and the increased tumor oxygenation can enhance the therapeutic effect of RT. In vitro experiments show that MZF-HA is able to achieve excellent specific targeting performance toward A549 cells with excellent biocompatibility as well as enhanced therapy performance under HT and RT in vitro by apoptosis flow cytometry. In the A549 subcutaneous tumor xenografts model, MRI confirms the enrichment of MZF-HA in tumor, and hypoxia immunohistochemistry analysis (IHC) proved the increased tumor oxygenation after HT. Furthermore, the tumor volume decreases to 49.6% through the combination of HT and RT in comparison with the 58.8% increase of the untreated group. These results suggest that the application of MZF-HA is able to increase the therapeutic effect of RT on A549 and can be used for further clinical NSCLC treatment evaluation.
Meiqi Chang,Wei Feng,Li Ding,Hongguang Zhang,Caihong Dong,Yu Chen,Jianlin Shi
Tumor oxygenation level has been regarded as an attractive target to elevate the efficiency of photodynamic therapy (PDT). Cyanobacterial photosynthesis-mediated reversal of tumor hypoxia could enable an oxygen-boosted PDT, but is limited by scant penetration depth and efficiency of external light. Herein, aiming at the dual purposes of reducing biological toxicity induced by long-term light irradiation and alleviating hypoxia, we here introduce a novel-designed CaAl 2 O 4 :Eu,Nd blue persistent luminescence material (PLM) as the in vivo light source after pre-excited in vitro . The ingenious construction of blue-emitting PLM with “optical battery” characteristics activates cyanobacterial cells and verteporfin simultaneously, which performs the successive oxygen supply and singlet oxygen generation without the long-term external excitation, resulting in the modulated tumor hypoxic microenvironment and enhanced photodynamic tumor proliferation inhibition efficiency. Both in vitro cellular assessment and in vivo tumor evaluation results affirm the advantages of self-produced oxygen PDT system and evidence the notable antineoplastic outcome. This work develops an irradiation-free photosynthetic bacteria-based PDT platform for the optimization of both oxygen production capacity and light utilization efficiency in cancer treatment, which is expected to promote the clinical progress of microbial-based photonic therapy.
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