Positron Emission Tomography-Guided Photodynamic Therapy with Biodegradable Mesoporous Silica Nanoparticles for Personalized Cancer Immunotherapy.
Positron Emission Tomography-Guided Photodynamic Therapy with Biodegradable Mesoporous Silica Nanoparticles for Personalized Cancer Immunotherapy.
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DOI：
10.1021/acsnano.9b06691
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发表时间：
2019-09
期刊：
影响因子：
17.1
通讯作者：
Cheng Xu;Jutaek Nam;Hao Hong;Yao Xu;J. Moon
中科院分区：
文献类型：
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作者：
Cheng Xu;Jutaek Nam;Hao Hong;Yao Xu;J. Moon
光动力疗法(PDT)是一种针对局部肿瘤的有效的、非侵入性的治疗方式，可以利用光源进行治疗。然而，将光动力疗法应用于播散性、转移性癌症的治疗仍然具有挑战性。另一方面，癌症免疫治疗为产生针对播散性癌症的全身性抗肿瘤免疫反应提供了一种很有前途的方法。在这里，我们报告了一种多功能纳米材料系统，用于PDT和个性化癌症免疫治疗的结合，并展示了它们对局部和播散性肿瘤的效力。具体地说，我们合成了均匀的、可生物降解的介孔二氧化硅纳米颗粒(BMSN)，其平均尺寸为~80 nm，大孔尺寸为5-10 nm，用于治疗正电子发射断层扫描(PET)引导的PDT和基于新抗原的肿瘤疫苗。多个新抗原肽、CpG寡核苷酸佐剂和光敏剂氯化e6共负载到bMSN纳米平台上，PET成像显示静脉注射后bMSN在肿瘤中有效积聚(高达9.0%ID/g)。随后激光照射的光动力疗法将树突状细胞招募到光动力疗法治疗的肿瘤部位，并激发出新抗原特异性的、肿瘤浸润性的CTL。使用多种小鼠双侧肿瘤模型，我们证明了PDT免疫疗法对局部治疗的肿瘤以及远处未治疗的肿瘤具有很强的抗肿瘤效果。我们的研究结果表明，bMSN是一个很有前途的平台，可以结合成像和PDT增强的个性化免疫治疗来治疗晚期癌症。
Photodynamic therapy (PDT) is an effective, non-invasive therapeutic modality against local tumors that are accessible to the source of light. However, it remains challenging to apply PDT for the treatment of disseminated, metastatic cancer. On the other hand, cancer immunotherapy offers a promising approach for generating systemic anti-tumor immune responses against disseminated cancer. Here we report a multifunctional nanomaterial system for the combination of PDT and personalized cancer immunotherapy and demonstrate their potency against local as well as disseminated tumors. Specifically, we have synthesized uniform and biodegradable mesoporous silica nanoparticles (bMSN) with an average size of ~80 nm and large pore size of 5-10 nm for theranostic positron emission tomography (PET)-guided PDT and neoantigen-based cancer vaccination. Multiple neoantigen peptides, CpG oligodeoxynucleotide adjuvant, and photosensitizer chlorin e6 were co-loaded into bMSN nanoplatform, and PET imaging revealed effective accumulation of bMSN in tumors (up to 9.0% ID/g) after intravenous administration. Subsequent PDT with laser irradiation recruited dendritic cells to PDT-treated tumor sites and elicited neoantigen-specific, tumor-infiltrating CTLs. Using multiple murine models of bilateral tumors, we demonstrate strong anti-tumor efficacy of PDT-immunotherapy against locally treated tumors as well as distant, untreated tumors. Our findings suggest that bMSN is a promising platform for combining imaging and PDT-enhanced personalized immunotherapy for the treatment of advanced cancer.