基于黑磷量子点的光热效应在树突状细胞激活中的作用
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摘要
癌症的免疫治疗是近年来兴起的一种治疗癌症的方法,通过人为地激活免疫系统来产生持久地杀伤肿瘤细胞的免疫反应,肿瘤疫苗是其最发达的部分之一。虽然目前肿瘤疫苗已经取得了很多突破,但仍然面临着巨大的挑战。在本研究中,采用癌细胞膜囊泡(cancer cell membrane nanovesicle, CCNVs)包裹黑磷量子点(black phosphorus quantum dots, BPQDs)制备得到负载黑磷量子点的癌细胞膜囊泡(BPQD-CCNVs),并将从小鼠骨髓中分离得到的树突状细胞与BPQD-CCNVs共同孵育,然后用808 nm近红外光对培养基照射10 min,最后用流式细胞分析仪检测树突状细胞表面分子CD80、CD86和MHC-II的表达情况。所有动物实验均经过清华大学动物伦理委员会批准。结果表明,基于黑磷量子点的光热效应能使培养基的温度升高,刺激树突状细胞成熟,使树突状细胞表面CD80、CD86和MHC-II的表达上调。本研究证明光热作用可以刺激树突状细胞的成熟。因此,可将光热作用引入到肿瘤疫苗中,增强肿瘤疫苗激活免疫系统的能力。
Immunotherapy is the most active research area for cancer treatment. Tumor vaccine is one of the most developed aspects of cancer immunotherapy. Though tumor vaccine has made many breakthrough, it still faces many challenges. In this study, we coated the black phosphorus quantum dots(BPQDs) with cancer cell membrane to create a nanoparticle named BPQD-CCNVs. The BPQD-CCNVs were incubated with bone marrowderived dendritic cells and irradiated with 808 nm infrared light. We tested the expression level of CD80, CD86 and MHC II of dendritic cells by flow cytometry after irradiation. All animal experiments approved by the Animal Experiments Ethical Committee of Tsinghua University. The results showed that the rise of medium's temperature caused by the photothermal effect of BPQDs could upregulate the expression of CD80, CD86 and MHC-II on dendritic cell surface. Based on these, we conclude that near infrared irradiation can stimulate the activation of dendritic cells. Our study may have provided a new strategy for tumor vaccine development.
Immunotherapy is the most active research area for cancer treatment. Tumor vaccine is one of the most developed aspects of cancer immunotherapy. Though tumor vaccine has made many breakthrough, it still faces many challenges. In this study, we coated the black phosphorus quantum dots(BPQDs) with cancer cell membrane to create a nanoparticle named BPQD-CCNVs. The BPQD-CCNVs were incubated with bone marrowderived dendritic cells and irradiated with 808 nm infrared light. We tested the expression level of CD80, CD86 and MHC II of dendritic cells by flow cytometry after irradiation. All animal experiments approved by the Animal Experiments Ethical Committee of Tsinghua University. The results showed that the rise of medium's temperature caused by the photothermal effect of BPQDs could upregulate the expression of CD80, CD86 and MHC-II on dendritic cell surface. Based on these, we conclude that near infrared irradiation can stimulate the activation of dendritic cells. Our study may have provided a new strategy for tumor vaccine development.
引文
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[2]Zhao ZJ,Chen Y,Francisco NM,et al.The application of CAR-T cell therapy in hematological malignancies:advantages and challenges[J].Acta Pharm Sin B,2018,8:539-551.
[3]Baumeister SH,Freeman GJ,Dranoff G,et al.Coinhibitory pathways in mmunotherapy for cancer[J].Annu Rev Immunol,2016,34:539-573.
[4]Hwang WL,Pike L,Royce TJ,et al.Safety of combining radio‐therapy with immune-checkpoint inhibition[J].Nat Rev Clin Oncol,2018,15:477-494.
[5]Sahin U,Tureci O.Personalized vaccines for cancer immuno‐therapy[J].Science,2018,359:1355-1360.
[6]Newick K,O'Brien S,Moon E,et al.CAR T cell therapy for solid tumors[J].Annu Rev Med,2017,68:139-152.
[7]Drake CG,Lipson EJ,Brahmer JR.Breathing new life into immunotherapy:review of melanoma,lung and kidney cancer[J].Nat Rev Clin Oncol,2014,11:24-37.
[8]Lubaroff DM.Prostate cancer vaccines in clinical trials[J].Expert Rev Vaccines,2012,11:857-868.
[9]Coulie PG,Van den Eynde BJ,van der Bruggen P,et al.Tumour antigens recognized by T lymphocytes:at the core of cancer immunotherapy[J].Nat Rev Cancer,2014,14:135-146.
[10]Liu YF,Xue XX,Li ZY,et al.Effect of apigenin on dendritic cells maturation and function in murine splenocytes[J].Acta Pharm Sin(药学学报),2017,52:397-402.
[11]Gusmao R,Sofer Z,Pumera M.Black phosphorus rediscovered:from bulk material to monolayers[J].Angew Chem Int Ed Engl,2017,56:8052-8072.
[12]Gui R,Jin H,Wang Z,et al.Black phosphorus quantum dots:synthesis,properties,functionalized modification and applica‐tions[J].Chem Soc Rev,2018,47:6795-6823.
[13]Tao W,Zhu X,Yu X,et al.Black phosphorus nanosheets as a robust delivery platform for cancer theranostics[J].Adv Mater,2017.DOI:10.1002/adma.201603276.
[14]Liang X,Ye X,Wang C,et al.Photothermal cancer immuno‐therapy by erythrocyte membrane-coated black phosphorus for‐mulation[J].J Control Release,2019,296:150-161.
[15]Yee C,Lizee GA.Personalized therapy:tumor antigen discovery for adoptive cellular therapy[J].Cancer J,2017,23:144-148.
[16]Mahoney KM,Rennert PD,Freeman GJ.Combination cancer immunotherapy and new immunomodulatory targets[J].Nat Rev Drug Discov,2015,14:561-584.
[17]Kastenmuller W,Kastenmüller K,Kurts C,et al.Dendritic celltargeted vaccines--hope or hype?[J].Nat Rev Immunol,2014,14:705-711.
[18]Yamada A,Sasada T,Noguchi M,et al.Next-generation peptide vaccines for advanced cancer[J].Cancer Sci,2013,104:15-21.
[19]Aurisicchio L,Ciliberto G.Genetic cancer vaccines:current status and perspectives[J].Expert Opin Biol Ther,2012,12:1043-1058.
[20]Steinman RM.Decisions about dendritic cells:past,present,and future[J].Annu Rev Immunol,2012,30:1-22.
[21]Song Q,Zhang CD,Wu XH.Therapeutic cancer vaccines:from initial findings to prospects[J].Immunol Lett,2018,196:11-21.
[22]Evans SS,Repasky EA,Fisher DT.Fever and the thermal regula‐tion of immunity:the immune system feels the heat[J].Nat Rev Immunol,2015,15:335-349.