Photothermal Combined Immunotherapy Of Food Allergy Based On Polydopamine Nanocarriers

Allergen-specific immunotherapy(AIT),as a long-term immunotherapy method that can effectively correct the natural course of allergic diseases,has shown a very good application prospect in the desensitization treatment of food allergy.However,the current limitations of AIT such as low antigen utilization,potential systemic side effects,and weak immune response hinder its development.In AIT,dendritic cells(DC)act as professional antigen-presenting cells,and their maturation and differentiation have profound effects on initiating and activating T cell immune responses.In recent years,photothermal therapy(PTT)has been found to effectively promote the activation,maturation and differentiation of DC,and has the convenience of spatiotemporal controllability.Nanocarriers with photothermal effect can serve as the photothermal conversion unit for photothermal therapy,as well as improve the delivery efficiency of target loads.For food allergy AIT,it is unknown whether the photothermal effect of nanocarriers can be used to promote the controllable activation and maturation and differentiation of DC cells,thereby achieving the improvement of the efficacy of AIT.In view of this,this study took the polydopamine nanocarriers(PDA NP)with photothermal effect as a model to explore the feasibility of DC-mediated photothermal combined immune tolerance therapy.The main research contents are as follows:(1)Ovalbumin(OVA)was employed as the representative allergen.The OVA-Cp G nanocore that adsorbed with ammonium bicarbonate was loaded into PDA shell through onsurface polymerization of dopamine.The OVA@PDA NPs had a spherical morphology with a size of about 170 nm.Under the irradiation of 808 nm near-infrared light,the OVA@PDA NPs showed photothermal conversion ability and thermal triggered release of the OVA-Cp G cargo.(2)The results of in vitro cell experiments showed that the light conditions used in the experiment and the dose of OVA@PDA NP had no obvious toxic and side effects on bone marrow DCs.Confocal experiments showed that OVA@PDA significantly promoted the release of OVA antigens under light conditions.Flow cytometry analysis showed that OVA signal in bone marrow DC cells increased significantly after phototermal treatment.Meanwhile,it was found that OVA@PDA NPs combined with photothermal treatment could significantly promote the maturation and differentiation of bone marrow DCs.(3)The results of in vivo experiments in mice show that after subcutaneous injection of OVA@PDA NPs,they can achieve hyperthermia of 42 °C under the irradiation of near-infrared light at 808 nm.In vivo fluorescence imaging showed that the retention rate of OVA@PDA NP in mice was still high after 48 h,and the photothermal effect can effectively promote the exposure of OVA antigen.After photothermal combined with immune tolerance treatment,serum and spleen-related indicators showed that OVA@PDA NP combined with photothermal therapy could promote the shift of Th1/Th2 balance toward Th1,and the proportion of Treg cells increased,which successfully promoted the body’s immune tolerance to OVA and relieved allergic symptoms in mice.