A versatile photothermal vaccine based on acid-responsive glyco-nanoplatform for synergistic therapy of cancer.
A versatile photothermal vaccine based on acid-responsive glyco-nanoplatform for synergistic therapy of cancer.
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DOI：
10.1016/j.biomaterials.2021.120792
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发表时间：
2021-06
期刊：
影响因子：
14
通讯作者：
Wu X
中科院分区：
文献类型：
--
作者：
Gao Y;Zhao Q;Xiao M;Huang X;Wu X
阻止癌症的治疗药物的竞争正在进行。有效的疫苗为癌症免疫治疗提供了一种安全且有前途的方法。然而，癌症疫苗中免疫治疗的实质性障碍包括癌症抗原的低免疫原性和实体瘤中通常存在的免疫抑制，导致开发临床有效的癌症疫苗面临重大挑战。在这里，研究了协同治疗的最新技术水平，其包括光热效应与免疫治疗的组合，以靶向肿瘤。首次将吲哚菁绿色（ICG，称为I）、咪喹莫特（R837，称为R）和具有来自卵清蛋白（OVA）的SIINFEKL序列的外源细胞毒性T淋巴细胞抗原肽（CTL-Ap，称为Ap）用缩醛化葡聚糖（AcDEX）包封以形成平均直径为92 nm的纳米颗粒（NPs）作为免疫原。施用所得多功能疫苗I-R-Ap-AcDEX NP增强了抗肿瘤细胞毒性T淋巴细胞（CTL）免疫疗法。一方面，皮下免疫的NP允许外来的Ap进入抗原呈递细胞的主要组织相容性复合物I类（MHC-I）交叉呈递途径，从而呈递Ap并引发高水平的Ap特异性CTL。另一方面，瘤内/静脉内注射NP允许外源Ap进入肿瘤细胞并通过MHC-I交叉呈递途径呈递Ap。Ap特异性CTL可以杀伤Ap呈递的肿瘤细胞。此外，纳米粒子产生的近红外激光触发了肿瘤细胞的光热杀伤。据我们所知，这是AcDEX纳米粒在抗肿瘤光热治疗中的首次报道。引人注目的是，当应用于两种非OVA肿瘤模型时，I-R-Ap-AcDEX NP与近红外激光照射组合的全身施用允许对小鼠完全保护免于肿瘤。这一令人印象深刻的结果显示了疫苗I-R-Ap-AcDEX NPs协同治疗的巨大前景，这是一种利用光热效应促进抗肿瘤免疫治疗的方法。
The race is on for therapeutic agents that stop cancer. An effective vaccine offers a safe and promising approach for cancer immunotherapy. However, substantial barriers to immunotherapy in cancer vaccines include the low immunogenicity of cancer antigens and the immunosuppression commonly present in solid tumors, resulting in significant challenges for developing a clinically effective cancer vaccine. Here, the state of the art of synergistic therapy, which includes the photothermal effect combined with immunotherapy, was investigated to target tumors. For the first time, indocyanine green (ICG, referred to as I), imiquimod (R837, referred to as R) and a foreign cytotoxic T lymphocyte antigen peptide (CTL-Ap, referred to as Ap) with the sequence of SIINFEKL from ovalbumin (OVA) were encapsulated by acetalated dextran (AcDEX) to form nanoparticles (NPs) averaging 92 nm in diameter as an immunogen. Administration of the resulting multifunctional vaccine I-R-Ap-AcDEX NPs enhanced antitumor cytotoxic T lymphocyte (CTL) immunotherapy. On the one hand, subcutaneous immunization of the NPs allows foreign Ap to enter the major histocompatibility complex class I (MHC-I) cross-presentation pathway of antigen-presenting cells, thereby presenting Ap and eliciting high levels of Ap-specific CTLs. On the other hand, intratumor/intravenous injections of the NPs allow foreign Ap to enter tumor cells and present Ap through the MHC-I cross-presentation pathway. Ap-specific CTLs can kill Ap-presented tumor cells. Furthermore, the NPs generated near-infrared laser triggered the photothermal killing of tumor cells. To our knowledge, this is the first report of AcDEX NPs in antitumor photothermal therapy. Strikingly, systemic administration of the I-R-Ap-AcDEX NPs combined with near-infrared laser irradiation allowed for complete protection to mice from the tumors when applied to two non-OVA tumor models. This quite impressive result displays the great promise of synergistic therapy by the vaccine I-R-Ap-AcDEX NPs, an approach that harnesses the photothermal effect to boost antitumor immunotherapy.
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影响因子：
4.9
作者：
Collier MA;Junkins RD;Gallovic MD;Johnson BM;Johnson MM;Macintyre AN;Sempowski GD;Bachelder EM;Ting JP;Ainslie KM
通讯作者：
Ainslie KM
DOI：
10.1073/pnas.0901592106
发表时间：
2009-04-07
影响因子：
11.1
作者：
Broaders, Kyle E.;Cohen, Joel A.;Frechet, Jean M. J.
通讯作者：
Frechet, Jean M. J.
近红外染料结合白蛋白具有独立的成像和治疗波长通道，用于成像引导光热治疗
影响因子：
14
作者：
Chen, Qian;Wang, Chao;Liu, Zhuang
通讯作者：
Liu, Zhuang
影响因子：
46.2
作者：
Jung HS ;Verwilst P ;Sharma A ;Shin J ;Sessler JL ;Kim JS
通讯作者：
Kim JS
影响因子：
18.2
作者：
Cha BG;Jeong JH;Kim J
通讯作者：
Kim J