Background Several recent studies have well demonstrated that the chemotherapy or near-infrared-II (NIR-II) photothermal therapy (PTT) can induce immunogenic cell death (ICD). However, single treatment based on the independent chemotherapy or PTT to induce ICD may require high dose of drug, high laser power, or high temperature, which limits their clinical application. We hypothesize that combination of chemotherapy and NIR-II PTT possesses great promise to overcome respective limitations. This manuscript describes the development of polyethylene glycol (PEG) modified hollow CuxS nanoparticles (NPs) for synergistic chemo-photothermal therapy to effectively promote ICD.
Results Hollow structure CuxS-PEG NPs were prepared under mild condition by using Cu2O NPs as sacrificial templates. CuxS loaded with doxorubicin (Dox) as NDDSs were characterized for hydrate particle size and surface charge. The morphology, photothermal effect, drug loading/releasing abilities, synergistic chemo-photothermal therapy, and ICD from synergistic therapy of CuxS-PEG NPs have been investigated. The in vitro outcomes of ICD and chemo-photothermal therapy were assessed in EMT-6 cells. In vivo therapeutic studies and immunoreaction were performed in EMT-6 bearing mice where therapeutic outcomes were assessed by tumor volume, immunohistochemical staining, and expression of CD8+ cytotoxic T-lymphocytes. The CuxS-PEG NPs with hollow structure show high drug loading capacity (~255 μg Dox per mg of CuxS NPs) and stimuli-responsive drug release triggered by NIR-II laser irradiation. The chemo-photothermal strategy more effectively induces ICD than that of the single treatment, accompanying with the release of adenosine triphosphate, pre-apoptotic calreticulin, and high mobility group box-1. Finally, the synergistic chemo-photothermal therapy based on the Dox/CuxS-PEG NPs promotes CD8+ cytotoxic T-lymphocytes infiltration into tumors and achieves ~98.5% tumor elimination.
Conclusion Therefore, our study emphasizes that the great potentials of CuxS-PEG NPs can be used as NIR-II light-responsive NDDSs for the applications of biomedicine and immunotherapy.
