Ferroptosis-apoptosis combined anti-melanoma immunotherapy with a NIR-responsive upconverting mSiO2 photodynamic platform
Ferroptosis-apoptosis combined anti-melanoma immunotherapy with a NIR-responsive upconverting mSiO2 photodynamic platform
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DOI：
10.1016/j.cej.2021.129557
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发表时间：
2021-04-08
影响因子：
15.1
通讯作者：
Tao, Juan
中科院分区：
文献类型：
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作者：
Li, Danqi;Ren, Jingli;Tao, Juan
光动力学疗法（PDT）因其高度的时空选择性和无创性而成为治疗肿瘤性皮肤病的一种有吸引力的方法。但由于紫外-可见光的穿透深度有限、黑色素的光学过滤作用和免疫原性弱等原因，限制了其在黑色素瘤中的应用。为了克服不完全的肿瘤损伤和抗肿瘤免疫不足的问题，我们制备了介孔包覆的上转换纳米颗粒（NaYF 4：Yb，Er@NaYF4@mSiO（2）@lipsome）平台，通过共沉淀二氢卟酚e6（Ce 6）和丁硫基亚砜亚胺（BSO）。该平台将近红外（NIR）光转换为紫外-可见光，从而能够破坏深层病灶，放大铁凋亡和凋亡细胞死亡，以及提高抗肿瘤免疫力。在近红外激光照射下，Ce 6包埋的NaYF 4：Yb，Er@NaYF4@mSiO（2）@脂质体纳米粒子通过提高羟基自由基水平和诱导细胞凋亡来减轻肿瘤部位的负担。同时，谷胱甘肽耗竭诱导通过BSO共同管理和直接硫醇氧化，然后通过脂质过氧化物修复酶的失活和铁凋亡的启动。这种组合策略导致肿瘤内氧化应激放大，这伴随着强烈的细胞毒性在体外和体内。抗肿瘤性能的恶化导致损伤相关分子模式的暴露，随后促进树突状细胞的成熟和肿瘤浸润淋巴细胞的效应功能。总之，这种融合-凋亡结合的光动力学策略为设计用于黑色素瘤免疫治疗的纳米药物提供了见解。
Photodynamic therapy (PDT) is an appealing treatment for oncologic skin diseases owing to its high spatiotemporally selectivity and non-invasive features. However, its application in melanoma has been restricted by limited penetration depth of ultraviolet (UV)-visible (vis) light, melanin-optical filtration and weak immunogenicity. To circumvent the incomplete tumor damage and insufficient anti-tumor immunity, we prepared a mesoporous coated upconverting nanoparticles (NaYF4:Yb,Er@NaYF4@mSiO(2)@lipsome)-based platform by coloading chlorin e6 (Ce6) and buthionine sulfoximine (BSO). This platform converts near-infrared (NIR) light to UV-vis light which enables the destruction of deeply seated nidus, amplification of ferroptotic and apoptotic cell death, as well as an increase in the anti-tumor immunity. Under NIR laser irradiation, NaYF4:Yb, Er@NaYF4@mSiO(2)@lipsome nanoparticles embedded with Ce6 were designed to ease burden in tumor sites via elevating levels of hydroxyl radicals and the induction of apoptosis. Meanwhile, glutathione depletion was induced through BSO co-administration and direct thiol oxidation, followed by the inactivation of lipid peroxide repair enzyme and initiation of ferroptosis. This combinational strategy resulted in an amplification in intratumoral oxidative stress, which was accompanied with the strong cytotoxicity in vitro and in vivo. The aggravated anti-tumor performance then brought about the exposure of damage-associated molecular patterns, followed by promoted maturation of dendritic cells and effector function of tumor-infiltrating lymphocytes. Taken together, this fermptosis-apoptosis combined photodynamic strategy provides insights in designing nanomedicines for immunotherapy in melanoma.