Immunogenic-cell-killing and immunosuppression-inhibiting nanomedicine.
Immunogenic-cell-killing and immunosuppression-inhibiting nanomedicine.
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免疫原性细胞杀伤和免疫抑制纳米药物
DOI：
10.1016/j.bioactmat.2020.11.016
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发表时间：
2021-06
影响因子：
18.9
通讯作者：
Yang Z
中科院分区：
文献类型：
--
作者：
Wang Y;Gao D;Liu Y;Guo X;Chen S;Zeng L;Ma J;Zhang X;Tian Z;Yang Z
将化学治疗与免疫检查点抑制剂相结合有助于杀死癌细胞并通过抑制免疫逃逸激活免疫系统。然而，由于药物和抑制剂在某些肿瘤组织中的累积受损，它们的治疗效果仍然有限。本文采用一种新型的基于聚（丙烯酰胺-丙烯腈-乙烯基咪唑-双（2-甲基丙烯酰基）氧乙基二硫醚）（PAAVB）聚合物的智能平台，具有可控的上临界溶解温度（UCST），用于紫杉醇（PTX）和姜黄素（CUR）的同时递送。此外，透明质酸（HA）层涂覆在PAAVB纳米颗粒的表面上，以靶向CD 44过表达的肿瘤细胞。所提出的纳米药物在肿瘤组织中表现出令人满意的积累，并被癌细胞吸收。然后，癌细胞中的酸性微环境和高水平的谷胱甘肽（GSH）可以自发地降低聚合物的UCST，导致纳米颗粒的分解和在体温下的快速药物释放，而无需额外的刺激。PTX和CUR分别通过抑制吲哚胺2，3-双加氧酶1（IDO 1）的活性，诱导免疫原性细胞死亡（ICD），促进适应性抗肿瘤免疫原性，抑制免疫抑制。因此，这种智能纳米药物的协同作用可以抑制原发性乳腺肿瘤的生长并抑制其肺转移。具有可控上临界溶液温度（UCST）的智能纳米平台，用于同时靶向递送紫杉醇和姜黄素，以实现免疫原性细胞死亡和逆转免疫抑制。合成了一种具有pH和GSH可调控的上临界溶解温度（UCST）的新型共聚物PAAVB.开发了具有PAAVB共聚物核和HA壳的纳米平台，并显示出递送PTX和CUR的能力。PTX诱导的ICD和CUR诱导的IDO 1活性抑制协同刺激抗肿瘤免疫应答。智能纳米药物的协同作用可以抑制原发性乳腺肿瘤的生长并抑制其肺转移。
Combining chemo-therapeutics with immune checkpoint inhibitors facilitates killing cancer cells and activating the immune system through inhibiting immune escape. However, their treatment effects remain limited due to the compromised accumulation of both drugs and inhibitors in certain tumor tissues. Herein, a new poly (acrylamide-co-acrylonitrile-co-vinylimidazole-co-bis(2-methacryloyl) oxyethyl disulfide) (PAAVB) polymer-based intelligent platform with controllable upper critical solution temperature (UCST) was used for the simultaneous delivery of paclitaxel (PTX) and curcumin (CUR). Additionally, a hyaluronic acid (HA) layer was coated on the surface of PAAVB NPs to target the CD44-overexpressed tumor cells. The proposed nanomedicine demonstrated a gratifying accumulation in tumor tissue and uptake by cancer cells. Then, the acidic microenvironment and high level of glutathione (GSH) in cancer cells could spontaneously decrease the UCST of polymer, leading to the disassembly of the NPs and rapid drug release at body temperature without extra-stimuli. Significantly, the released PTX and CUR could induce the immunogenic cell death (ICD) to promote adaptive anti-tumor immunogenicity and inhibit immunosuppression through suppressing the activity of indoleamine 2,3-dioxygenase 1 (IDO1) enzyme respectively. Therefore, the synergism of this intelligent nanomedicine can suppress primary breast tumor growth and inhibit their lung metastasis. An intelligent nano-platform with controllable upper critical solution temperature (UCST) for simultaneous targeted delivery of paclitaxel and curcumin to achieve immunogenic cell death and reverse immunosuppression. A new copolymer PAAVB was prepared with pH- and GSH- controllable upper critical solution temperature (UCST) properties. A nano-platform with PAAVB copolymer core and HA shell was developed and showed the capability to deliver PTX and CUR. The antitumor immune response was synergistically stimulated by PTX-induced ICD and CUR induced IDO1activity suppression. The synergism of intelligent nanomedicine could suppress the primary breast tumor growth and inhibit their lung metastasis.
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影响因子：
8.8
作者：
Holmgaard RB;Zamarin D;Li Y;Gasmi B;Munn DH;Allison JP;Merghoub T;Wolchok JD
通讯作者：
Wolchok JD
影响因子：
--
作者：
Litzenburger UM;Opitz CA;Sahm F;Rauschenbach KJ;Trump S;Winter M;Ott M;Ochs K;Lutz C;Liu X;Anastasov N;Lehmann I;Höfer T;von Deimling A;Wick W;Platten M
通讯作者：
Platten M
无载体 HCPT/DOX 纳米药物通过改善细胞药物积累协同增强对乳腺癌细胞的治疗效果
影响因子：
4.9
作者：
Chen, Fei;Zhao, Yuanyuan;Liang, Xing-Jie
通讯作者：
Liang, Xing-Jie
加载近红外探针的肿瘤穿透纳米疗法可抑制乳腺癌的生长和转移
影响因子：
19
作者：
He, Xinyu;Bao, Xiaoyue;Li, Yaping
通讯作者：
Li, Yaping
影响因子：
19
作者：
Dai, Liangliang;Li, Ke;Cai, Kaiyong
通讯作者：
Cai, Kaiyong