An immunostimulatory dual-functional nanocarrier that improves cancer immunochemotherapy.
An immunostimulatory dual-functional nanocarrier that improves cancer immunochemotherapy.
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DOI：
10.1038/ncomms13443
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发表时间：
2016-11-07
影响因子：
16.6
通讯作者：
Li S
中科院分区：
文献类型：
--
作者：
Chen Y;Xia R;Huang Y;Zhao W;Li J;Zhang X;Wang P;Venkataramanan R;Fan J;Xie W;Ma X;Lu B;Li S
免疫化学疗法将化学治疗剂与免疫调节剂组合，代表了改善癌症治疗的有吸引力的方法。然而，免疫化疗的成功受到缺乏有效地将两种治疗剂共同递送至肿瘤的策略的阻碍。在这里，我们报告了一种双功能的免疫刺激性纳米胶束载体的开发，该载体基于PEG与NLG 919的前药缀合物，NLG 919是一种吲哚胺2，3-双加氧酶（IDO）抑制剂，目前用于逆转肿瘤免疫抑制。一个Fmoc基团，一个有效的药物相互作用的基序，也被引入到载体中，以提高药物负载能力和制剂稳定性。我们表明，PEG 2k-Fmoc-NLG单独在增强T细胞免疫应答方面是有效的，并且在体内表现出显著的抗肿瘤活性。更重要的是，使用PEG 2k-Fmoc-NLG纳米载体全身递送紫杉醇（PTX）导致乳腺癌和黑色素瘤小鼠模型中显著改善的抗肿瘤反应。 使用免疫刺激剂来增强化学疗法的功效是癌症治疗中有前途的策略。在这里，作者报告了一种胶束纳米颗粒，可以有效地共同提供化疗和免疫治疗，从而改善体内抗肿瘤反应。
Immunochemotherapy combines a chemotherapeutic agent with an immune-modulating agent and represents an attractive approach to improve cancer therapy. However, the success of immunochemotherapy is hampered by the lack of a strategy to effectively co-deliver the two therapeutics to the tumours. Here we report the development of a dual-functional, immunostimulatory nanomicellar carrier that is based on a prodrug conjugate of PEG with NLG919, an indoleamine 2,3-dioxygenase (IDO) inhibitor currently used for reversing tumour immune suppression. An Fmoc group, an effective drug-interactive motif, is also introduced into the carrier to improve the drug loading capacity and formulation stability. We show that PEG2k-Fmoc-NLG alone is effective in enhancing T-cell immune responses and exhibits significant antitumour activity in vivo. More importantly, systemic delivery of paclitaxel (PTX) using the PEG2k-Fmoc-NLG nanocarrier leads to a significantly improved antitumour response in both breast cancer and melanoma mouse models. The use of immunostimulatory agents to enhance the efficacy of chemotherapy is a promising strategy in cancer therapy. Here, the authors report on a micellar nanoparticle that can effectively co-deliver chemo- and immunotherapeutics, resulting in an improved in vivo antitumour response.