Abstract：
Tumor immunotherapy has emerged as an efficacious therapeutic approach that mobilizes the patient\'s immune system to achieve durable tumor suppression. Here, we design a photodynamic therapy-motivated nanovaccine (Dex-HDL/ALA-Fe3O4) co-delivering 5-aminolevulinic acid and Fe3O4 nanozyme that demonstrate a long-term durable immunotherapy strategy. After vaccination, the nanovaccine exhibits obvious tumor site accumulation, lymph node homing, and specific and memory antitumor immunity evocation. Upon laser irradiation, Dex-HDL/ALA-Fe3O4 effectively generates reactive oxygen species at the tumor site not only to induce the immunogenic cell death-cascade but also to trigger the on-demand release of full types of tumor antigens. Intriguingly, Fe3O4 nanozyme-catalyzed hydrogen peroxide generated oxygen for alleviating tumor hypoxia and modifying the inhibitory tumor microenvironment, thereby exhibiting remarkable potential as a sensitizer. The intravenous administration of nanovaccines in diverse preclinical cancer models has demonstrated remarkable tumor regression and inhibition of postoperative tumor recurrence and metastasis, thereby enabling personalized treatment strategies against highly heterogeneous tumors.
摘要：
肿瘤免疫疗法已成为一种有效的治疗方法，可以动员患者的免疫系统来实现持久的肿瘤抑制。这里,我们设计了一种光动力疗法驱动的纳米疫苗(Dex-HDL/ALA-Fe3O4)共递送5-氨基乙酰丙酸和Fe3O4纳米酶,证明了一种长期持久的免疫治疗策略.接种疫苗后,纳米疫苗表现出明显的肿瘤部位积累，淋巴结归巢,和特异性和记忆抗肿瘤免疫唤起。激光照射后，Dex-HDL/ALA-Fe3O4在肿瘤部位有效地产生活性氧，不仅诱导免疫原性细胞死亡级联反应，而且触发全类型肿瘤抗原的按需释放。有趣的是，Fe3O4纳米酶催化过氧化氢产生的氧气用于缓解肿瘤缺氧和改变抑制性肿瘤微环境，从而表现出作为敏化剂的显著潜力。在不同的临床前癌症模型中静脉内施用纳米疫苗已经证明了显著的肿瘤消退和术后肿瘤复发和转移的抑制,从而实现针对高度异质性肿瘤的个性化治疗策略。
