SBIR Phase II: Manufacturing of Red Blood Cell Membrane-Coated Nanoparticles for detoxification

这个小企业创新研究（SBIR）二期项目的更广泛的影响/商业潜力是使红血膜涂层纳米颗粒平台的大规模生产成为可能，该平台先前被证明能够吸收和中和各种溶血性致病因素，如细菌毒素、动物毒液和自身反应性免疫球蛋白。纳米颗粒完全由生物相容性和可生物降解的材料组成，并由天然红细胞制成的细胞膜包裹，能够在循环中循环很长一段时间。它们的仿生外表使它们能够作为诱饵清除攻击细胞膜的毒力因子。纳米制剂可用于多种紧迫和未满足的医疗需求，包括动物中毒、自身免疫性溶血性疾病和细菌感染。制造工艺的成功开发也对纳米制造和纳米医学发展领域产生了更广泛的影响。该项目将使红血球膜包覆的纳米颗粒能够高效、可靠地大规模生产，并用于临床转化。为了确保制造的纳米制剂具有最佳的尺寸、均匀性、生物活性和性能，先进的流体学、过滤、显微镜和颗粒跟踪技术将应用于精确的纳米颗粒制备和表征。具体来说，拟议的研究活动将集中在具有一致物理化学性质的均匀聚合纳米颗粒的合成，纯化和不受破坏的红细胞膜的衍生，以及纳米颗粒底物上可靠的细胞膜涂层。所得到的纳米颗粒将被彻底检查，以迭代改进制备过程。将根据良好生产规范（GMP）为大规模生产高质量纳米制剂开发优化的生产方案。该项目将促进新型仿生纳米颗粒平台从实验室到床边的过渡，这对解决涉及蛋白质毒素的许多重大疾病具有重要意义。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase II project is enabling the large-scale manufacturing of a red blood cell membrane coated nanoparticle platform, which was previously demonstrated to be capable of absorbing and neutralizing a wide array of hemolytic pathogenic factors, such as bacterial toxins, animal venoms, and auto-reactive immunoglobulin. Comprised entirely of biocompatible and biodegradable materials and coated by cell membranes derived from natural red blood cells, the nanoparticles are able to circulate for an extended period of time in the circulation. Their biomimetic exterior allows them to serve as a decoy to scavenge virulence factors that attack cell membranes. The nanoformulation may be applied against multiple pressing and unmet medical needs, including animal envenoming, autoimmune hemolytic diseases, and bacterial infections. Successful development of the manufacturing process also has broader impact in the field of nanofabrication and nanomedicine development. The proposed project will enable the red blood cell membrane-coated nanoparticles to be manufactured efficiently and reliably at a large scale toward clinical translation. To ensure that the manufactured nanoformulations will have the optimal size, uniformity, biological activity, and performance, advanced fluidics, filtration, microscopy, and particle tracking techniques will be applied for precision nanoparticle preparation and characterization. Specifically, the proposed research activity will focus on the synthesis of uniform polymeric nanoparticles with consistent physicochemical properties, derivation of purified and undisrupted red blood cell membranes, and reliable cell membrane coating over the nanoparticle substrates. The resulting nanoparticles will be thoroughly examined to iteratively improve the preparation process. Optimized manufacturing protocol will be developed for large-scale production of high quality nanoformulations following good manufacturing practices (GMP). The project will facilitate the bench-to-bedside transition of the novel biomimetic nanoparticle platform, which has significant implications in addressing the many major diseases involving protein toxins.