Institute of Biomaterials and Biomedical Engineering , University of Toronto , Rosebrugh Building, Room 407, 164 College Street , Toronto , Ontario M5S 3G9 , Canada.
College of Chemistry & Chemical Engineering , Chongqing University of Science & Technology , University Town, Shapingba District, Chongqing 401331 , PR China.
Nano Lett. 2019 Jan 9;19(1):116-123. doi: 10.1021/acs.nanolett.8b03434. Epub 2018 Dec 28.
Nanoparticles are engineered from materials such as metals, polymers, and different carbon allotropes that do not exist within the body. Exposure to these exogenous compounds raises concerns surrounding toxicity, inflammation, and immune activation. These responses could potentially be mitigated by synthesizing nanoparticles directly from molecules derived from the host. However, efforts to assemble patient-derived macromolecules into structures with the same degree of size and shape tunability as their exogenous counterparts remains a significant challenge. Here we solve this problem by creating a new class of size- and shape-tunable personalized protein nanoparticles (PNP) made entirely from patient-derived proteins. PNPs are built into different sizes and shapes with the same degree of tunability as gold nanoparticles. They are biodegradable and do not activate innate or adaptive immunity following single and repeated administrations in vivo. PNPs can be further modified with specific protein cargos that remain catalytically active even after intracellular delivery in vivo. Finally, we demonstrate that PNPs created from different human patients have unique molecular fingerprints encoded directly into the structure of the nanoparticle. This new class of personalized nanomaterial has the potential to revolutionize how we treat patients and can become an integral component in the diagnostic and therapeutic toolbox.
纳米粒子是由金属、聚合物和不同的碳同素异形体等材料制成的，这些材料在体内并不存在。接触这些外源性化合物会引起人们对毒性、炎症和免疫激活的担忧。通过直接从宿主来源的分子合成纳米粒子，可以减轻这些反应。然而，将源自患者的生物大分子组装成具有与外源性类似物相同的尺寸和形状可调性的结构仍然是一个重大挑战。在这里，我们通过创建一类全新的、完全由患者来源的蛋白质制成的、尺寸和形状可调的个性化蛋白质纳米颗粒（PNP）来解决这个问题。PNP 可以构建成不同的尺寸和形状，具有与金纳米颗粒相同的可调性。它们是可生物降解的，并且在体内单次和重复给药后不会激活先天或适应性免疫。PNP 可以进一步用特定的蛋白质 cargos 进行修饰，即使在体内细胞内递送后，这些 cargos 仍然保持催化活性。最后，我们证明了由不同的人类患者产生的 PNP 具有直接编码在纳米颗粒结构中的独特分子指纹。这种新型的个性化纳米材料有可能彻底改变我们治疗患者的方式，并成为诊断和治疗工具包中的一个组成部分。
