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Zhu Xueqiong/Chen Tianfeng Biomaterials: Immunonanotherapy reprograms the immunosuppressive environment to make tumors "hot"





Low tumor mutation burden and lack of T cells in the tumor site are the typical features of "cold immune tumors" that paralyze the immune system. In order to activate anti-tumor immunity, the strategy of turning "cold tumors" into "hot tumors" to increase the infiltration of T cells has attracted widespread attention. Zhu Xueqiong, Second Medical University Affiliated to Wenzhou Medical University/Chen Tianfeng of Jinan University, produced immunogenic core-shell Au @ Se NP through the gold-selenium coordination bond to achieve nanoparticle-mediated local photothermal trigger immunotherapy.



Incorporating gold nanostars (AuNSs) with improved photothermal stability and transformation efficiency will promote the decomposition and transformation of selenium nanoparticles (SeNPs), thereby leading to increased apoptosis of cancer cells by generating higher temperatures. In addition, the results of in vivo experiments show that the synergy between SeNPs-mediated chemotherapy and AuNSs-induced photothermal therapy not only produces a local anti-tumor immune response with excellent cancer killing effects in the presence of tumor-associated antigens, It can also effectively reprogram M2 macrophages to M1 phenotypic transition, with the activity of phagocytosing distant tumors.


The Au @ Se NPs with strong photothermal efficiency and stability are synthesized by a simple and easy method, which can effectively promote the transformation of Se in the acidic environment of tumors, and has broad application prospects in future clinical cancer treatments. Compared with other PTT nanomedicines, AuNSs encapsulated by SeNPs have the following advantages: (i) Due to the plasma coupling of AuNSs, the thermal stability is improved, and the photothermal conversion efficiency is enhanced; (ii) NIR absorbed by Au @ Se NPs Effectively convert into heat to promote the conversion of SeNPs to SeCys by intensifying cell metabolism, thereby enhancing the induction of cancer cell apoptosis; (iii) PTT triggered by Au @ Se NPs can up-regulate Hsp70 as a recruiter of DC to promote antigen Cross-presentation triggers the infiltration of cytotoxic lymphocytes into the tumor; (iv) The synergy between SeNPs-mediated chemotherapy and AuNSs-induced PTT can reshape TAM from the M2 phenotype to the M1 phenotype to support T cell activation and Tumor kills. (V) The systemic immune response activated by Au @ Se NPs not only induces the regression of the primary tumor, but also avoids the invasion of distant tumors. All in all, this research expands the application of Au @ Se NPs as high-efficiency photothermal agents, and emphasizes innovative strategies for systemic cancer immunotherapy, thereby enhancing the immunity triggered by this simple and effective nanocomposite system in photothermal therapy Future applications in treatment.

NanoImmuno
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