Department of Orthopaedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China.
Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China.
J Nanobiotechnology. 2021 Aug 12;19(1):243. doi: 10.1186/s12951-021-00975-5.
The clinical treatment of metastatic spinal tumor remains a huge challenge owing to the intrinsic limitations of the existing methods. Programmed cell death protein 1 (PD1)/programmed cell death ligand 1 (PD-L1) pathway blockade has been explored as a promising immunotherapeutic strategy; however, their inhibition has a low response rate, leading to the minimal cytotoxic T cell infiltration. To ameliorate the immunosuppressive microenvironment of intractable tumor and further boost the efficacy of immunotherapy, we report an all-round mesoporous nanocarrier composed of an upconverting nanoparticle core and a large-pore mesoporous silica shell (UCMS) that is simultaneously loaded with photosensitizer molecules, the IDO-derived peptide vaccine AL-9, and PD-L1 inhibitor. The IDO-derived peptide can be recognized by the dendritic cells and presented to CD8 cytotoxic T cells, thereby enhancing the immune response and promoting the killing of the IDO-expressed tumor cells. Meanwhile, the near-infrared (NIR) activated photodynamic therapy (PDT) could induce immunogenic cell death (ICD), which promotes the effector T-cell infiltration. By combining the PDT-elicited ICD, peptide vaccine and immune checkpoint blockade, the designed UCMS@Pep-aPDL1 successfully potentiated local and systemic antitumor immunity and reduced the progression of metastatic foci, demonstrating a synergistic strategy for cancer immunotherapy.
由于现有方法的固有局限性,转移性脊柱肿瘤的临床治疗仍然是一个巨大的挑战。程序性细胞死亡蛋白 1(PD1)/程序性细胞死亡配体 1(PD-L1)通路阻断已被探索作为一种很有前途的免疫治疗策略;然而,它们的抑制作用反应率低,导致细胞毒性 T 细胞浸润很少。为了改善难治性肿瘤的免疫抑制微环境,并进一步提高免疫治疗的效果,我们报告了一种由上转换纳米颗粒核和大孔介孔二氧化硅壳(UCMS)组成的全方位介孔纳米载体,该载体同时负载光敏剂分子、IDO 衍生肽疫苗 AL-9 和 PD-L1 抑制剂。IDO 衍生肽可被树突状细胞识别并呈递给 CD8 细胞毒性 T 细胞,从而增强免疫反应,促进 IDO 表达肿瘤细胞的杀伤。同时,近红外(NIR)激活的光动力疗法(PDT)可诱导免疫原性细胞死亡(ICD),促进效应 T 细胞浸润。通过结合 PDT 诱导的 ICD、肽疫苗和免疫检查点阻断,设计的 UCMS@Pep-aPDL1 成功增强了局部和全身抗肿瘤免疫,并减少了转移性病灶的进展,为癌症免疫治疗提供了一种协同策略。
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