摘要
Objective::Immunotherapy is an effective tumor treatment strategy.However,its long treatment cycle limits its wide application across all cancer types.In this study,we optimized upconversion nanoparticles and manganese composite particles with a porous structure as a nanoplatform for synergistic photodynamic therapy(PDT)and photothermal therapy(PTT),and subsequent longer-term immunotherapy.Methods::The morphology,phase,and stability were first characterized to evaluate the biocompatibility of this material.The upconversion and near infrared II luminescence properties of the material and its stimuli-response effect were assessed from the absorbance and photoluminescence spectra.Phototherapy including PDT and PTT was demonstrated in vitro and in vivo,and immunotherapy was used to enhance the phototherapy.This study was approved by the Xi’an Jiaotong University,China(approval No.XJTULAC2020-585)on April 2,2020.Results::The nanoplatform showed good PDT and PTT effects with high upconversion luminescence,and exhibited a more sensitive glutathione response(detection limit:55μg/mL)using fluorescence recovery than that based on absorbance recovery,with the detection range extending up to 1.2 mg/mL.When the surface of the composite particles was modified with an anti-PD-L1 immune checkpoint inhibitor,it targeted A549 lung cancer cells.The resulting immune response enhanced the long-term anti-tumor effect of the therapy,especially in lung cancer patients with high PD-L1 expression.Conclusion::The designed composite can be simultaneously used to detect the glutathione concentration based on luminescence recovery in the tumor cells and as a theranostic nanoplatform for synergistic immuno-phototherapy when combined with an antibody.
基金
supported by the National Key Research and Development Program of China Grant(Nos.2017YFC1309100,2018YFC0910602,2017YFA0205202)
the Natural Science Foundation of China(Nos.81801744,91859202).
