Pluronic F127 "nanoarmor" for stabilization of Cowpea mosaic virus immunotherapy.

Pluronic F127 "nanoarmor" for stabilization of Cowpea mosaic virus immunotherapy.
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DOI:
10.1002/btm2.10574
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发表时间:
2024-01
影响因子:
7.4
通讯作者:
Steinmetz, Nicole F.
Steinmetz, Nicole F.
中科院分区:
工程技术2区
文献类型:
--
作者:
Shin, Matthew D.;Jung, Eunkyeong;Moreno-Gonzalez, Miguel A.;Ortega-Rivera, Oscar A.;Steinmetz, Nicole F.

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我们的实验室证明了瘤内豇豆花叶病毒(CPMV)作为原位疫苗是一种有效的抗肿瘤免疫疗法。当我们为人类临床翻译铺平道路时,制剂化学需要优化候选药物的长期储存。在这项工作中,利用Pluronic F127对CPMV进行纳米工程,以实现液体和凝胶配方,减轻长期储存过程中的结构变化和RNA释放。我们利用B16F10小鼠黑色素瘤模型,通过结合体外实验和体内疗效来评估CPMV - F127制剂的稳定性和生物活性。结果表明,在4°C、25°C和37°C的长时间热孵育下,F127液体和凝胶制剂均能保持CPMV的结构和功能。没有配方的热培养CPMV导致结构变化和较差的体内疗效。与之形成鲜明对比的是,当CPMV被配制并被F127“纳米装甲”保护时,其体内疗效得以保留。
Our lab demonstrated that intratumoral Cowpea mosaic virus (CPMV) is a potent antitumor immunotherapy when used as in situ vaccine. As we pave the way for human clinical translation, formulation chemistry needs to be optimized for long‐term storage of the drug candidate. In this work, CPMV was nanoengineered with Pluronic F127 to realize liquid and gel formulations which mitigate structural changes and RNA release during long‐term storage. We evaluated the CPMV‐F127 formulations for their stability and biological activity through a combination of in vitro assays and efficacy in vivo using a B16F10 murine melanoma model. Results demonstrate that both F127 liquid and gel formulations preserve CPMV structure and function following extended periods of thermal incubation at 4°C, 25°C, and 37°C. Heat‐incubated CPMV without formulation resulted in structural changes and inferior in vivo efficacy. In stark contrast, in vivo efficacy was preserved when CPMV was formulated and protected with the F127 “nanoarmor.”
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