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首页> 外文期刊>Advanced Functional Materials >Recyclable Cytokines on Short and Injectable Polylactic Acid Fibers for Enhancing T-Cell Function
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Recyclable Cytokines on Short and Injectable Polylactic Acid Fibers for Enhancing T-Cell Function

机译：短而可注射的聚乳酸纤维上的可回收细胞因子，可增强T细胞功能

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摘要

The current practice of cytokine-based immunotherapy relies on high doses and multiple injections of cytokine agents, which raises patients' inconvenience and economic burden. Here, sustainable and recyclable cytokine delivery based on short and injectable polymer fibers immobilized with interleukin (IL)-2 and IL-15 is demonstrated, which can be retained at the target tumor sites upon injection. In detail, electrospun polylactic acid (PLA) fibers are treated with aqueous ethanol solution for their dispersion, increasing the interfiber space for highly efficient biomolecule conjugation, and further immobilized with protein G via enzymatic dopamine coating. The protein C-immobilized PLA fibers are cut into short fibers using a microtome, and filtering is performed to collect injectable short PLA (sPLA) fibers with the lengths of 15-100 mu m. These sPLA fibers are further loaded with cytokines via the interaction between protein G and Fc, and cytokine-loaded sPLA (Cyto-sPLA) fibers are injected near the tumor sites using a syringe. The administration of Cyto-sPLA fibers efficiently suppresses the tumor growth up to 70% by reinvigorating nonfunctional T cells to a functional state that can kill tumors in a sustainable and recyclable manner. The injectable sPLA-fiber platform can be employed as a carrier for the efficient delivery of various agents in vivo.
机译：基于细胞因子的免疫疗法的当前实践依赖于高剂量和多次注射细胞因子剂，这增加了患者的不便和经济负担。在此，证明了基于固定有白介素（IL）-2和IL-15的短而可注射的聚合物纤维的可持续且可回收的细胞因子传递，注射后可保留在靶肿瘤部位。详细地，用乙醇水溶液处理静电纺丝聚乳酸（PLA）纤维以使其分散，增加纤维间空间以实现高效的生物分子缀合，并通过酶促多巴胺涂层将蛋白G固定化。使用切片机将固定有蛋白C的PLA纤维切成短纤维，并进行过滤以收集长度为15-100μm的可注射的短PLA（sPLA）纤维。这些sPLA纤维通过蛋白G和Fc之间的相互作用进一步加载了细胞因子，并使用注射器将负载细胞因子的sPLA（Cyto-sPLA）纤维注射到肿瘤部位附近。 Cyto-sPLA纤维的给药可通过使非功能性T细胞恢复至可以可持续且可循环利用的方式杀死肿瘤的功能状态，有效地抑制肿瘤的生长，最高可达70％。可注射的sPLA-纤维平台可以用作在体内有效递送各种药剂的载体。

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  • 来源
    《Advanced Functional Materials》 |2019年第14期|1808361.1-1808361.11|共11页
  • 作者

    Shin Hyun Mu; Ju Youngjun; Kim Gwanghun; Lee Jae Won; Seo Myung Won; Sim Ji Hyun; Yang Jusang; Noh Sora; Kim Jungbae; Kim Hang-Rae;

  • 作者单位

    Seoul Natl Univ, Coll Med, Dept Anat & Cell Biol, Seoul 03080, South Korea|Seoul Natl Univ, Coll Med, Dept Biomed Sci, Seoul 03080, South Korea|Seoul Natl Univ, Coll Med, Biomed Sci Project BK21Plus, Seoul 03080, South Korea|Seoul Natl Univ, Coll Med, Med Res Inst, Seoul 03080, South Korea;

    Korea Univ, Dept Chem & Biol Engn, Seoul 02841, South Korea;

    Seoul Natl Univ, Coll Med, Dept Anat & Cell Biol, Seoul 03080, South Korea|Seoul Natl Univ, Coll Med, Dept Biomed Sci, Seoul 03080, South Korea|Seoul Natl Univ, Coll Med, Biomed Sci Project BK21Plus, Seoul 03080, South Korea;

    Seoul Natl Univ, Coll Med, Dept Biomed Sci, Seoul 03080, South Korea;

    Seoul Natl Univ, Coll Med, Dept Anat & Cell Biol, Seoul 03080, South Korea;

    Seoul Natl Univ, Coll Med, Dept Anat & Cell Biol, Seoul 03080, South Korea;

    Korea Univ, Dept Chem & Biol Engn, Seoul 02841, South Korea;

    Korea Univ, Dept Chem & Biol Engn, Seoul 02841, South Korea;

    Korea Univ, Dept Chem & Biol Engn, Seoul 02841, South Korea;

    Seoul Natl Univ, Coll Med, Dept Anat & Cell Biol, Seoul 03080, South Korea|Seoul Natl Univ, Coll Med, Dept Biomed Sci, Seoul 03080, South Korea|Seoul Natl Univ, Coll Med, Biomed Sci Project BK21Plus, Seoul 03080, South Korea|Seoul Natl Univ, Coll Med, Med Res Inst, Seoul 03080, South Korea;

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  • 关键词

    cancer immunotherapy; cytokine delivery; electrospun fibers; enzymatic polydopamine coating; injectable fibers;

    机译：癌症免疫疗法;细胞因子递送;电纺丝纤维;酶促多巴胺涂层;可注射纤维;

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