Cargo-free particles of ammonio methacrylate copolymers: From pharmaceutical inactive ingredients to effective anticancer immunotherapeutics
Cargo-free particles of ammonio methacrylate copolymers: From pharmaceutical inactive ingredients to effective anticancer immunotherapeutics
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DOI：
10.1016/j.biomaterials.2018.02.053
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发表时间：
2018-06-01
期刊：
影响因子：
14
通讯作者：
Lamprecht, Alf
中科院分区：
文献类型：
--
作者：
Boushehri, Maryam Alsadat Shetab;Stein, Valentin;Lamprecht, Alf
纳米颗粒为抗癌免疫治疗和疫苗接种创造了令人兴奋的平台，尽管其固有的免疫调节特性仍未得到充分利用。甲基丙烯酸氨酯共聚物(AMC)是制药业公认的辅料和控释口腔制剂的组成部分。在这里，我们证明了A型和B型AMC(Eudradit(R)RL和RS)的纳米尺度赋予了这些可用于癌症治疗的非活性成分免疫刺激特性。这些颗粒诱导天然免疫细胞分泌各种促炎细胞因子和趋化因子。尽管其潜在的机制尚未完全揭示，但目前的工作证实了Toll样受体4(TLR4)和核因子kappaB(NF-kappa B)的部分参与。颗粒的促炎特性和细胞因子/趋化因子诱导谱的大小和电荷依赖性也被证明。在肿瘤免疫治疗的背景下，两周一次的瘤周纳米颗粒注射导致同基因结直肠肿瘤完全消退或显著抑制其生长，显著延长了荷瘤动物的生存时间。此外，在处理的动物中存在免疫记忆被建立。与成熟的化疗和免疫疗法相比，AMC纳米粒具有更好的经济性和相对安全性，并且能够作为药物靶向、疫苗接种和联合治疗的载体，因此AMC纳米粒(AMCNP)是癌症治疗领域进一步研究的有趣课题。(C)2018爱思唯尔有限公司。保留所有权利。
Nanoparticles create exciting platforms for anticancer immunotherapy and vaccination, though their inherent immunomodulatory properties have remained underexploited. Ammonio methacrylate co-polymers (AMC) are well-established excipients in pharmaceutical industry and components of controlled-release oral formulations. Here, we demonstrate that nanoscaling of type A and B AMC (Eudragit (R) RL and RS) endows these inactive ingredients immunostimulatory properties exploitable for cancer therapy. The particles induce the secretion of various pro-inflammatory cytokines and chemokines from the cells of innate immunity. Though the underlying mechanisms are not fully uncovered, the current work established the partial involvement of Toll-like Receptor 4 (TLR4) and Nuclear factor kappa B (NF-kappa B). The size and charge-dependency of the particles' pro-inflammatory properties and cytokine/chemokine induction profile was also demonstrated. Within the context of cancer immunotherapy, biweekly peritumoral nanoparticle injection led to a complete regression of the syngeneic colorectal tumor, or a significant growth retardation thereof, considerably extending the survival of tumor-bearing animals. Additionally, presence of the immunological memory in treated animals was established. Given their better economical and relatively safer profile compared to well-established chemo- and immunotheraputics, and their ability to serve as carriers for drug targeting, vaccination and combination therapy, AMC nanoparticles (AMCNP) are fascinating subjects for further research in the field of cancer therapy. (C) 2018 Elsevier Ltd. All rights reserved.