Abstract:
The protein corona effect has long been treated as the evil source behind delivery efficacy issues. In this study, this concept is challenged by showcasing that the protein corona can serve as a versatile functionalization approach to improve the delivery efficacy or mitigate nanocytotoxicity. To this end, the depleted serum is introduced to create nanomaterials carrying functionally distinct protein corona, referred to as PCylated nanomaterials. It is confirmed that the passivation with depleted serum helps reduce the toxicity and pro-inflammatory response. Furthermore, the same method can be leveraged to enhance the capacity of nanomaterials to undergo endocytosis as well as their potential as an agonist for the NF-κB pathways. The comparable stability of protein corona created by late and early-stage serum reveals that the chanceless interaction with nanomaterials, rather than an inadequate binding strength, may be behind the failure of enriching certain components. The PCylation strategy is extended to cancer patient-derived fluid, creating a set of T1 and T3-stage cancer-specific nanotherapeutics to retard the metastasis of cancer cells, while leaving normal endothelial negligibly affected. It is hoped the novel PCylation approach validated here can shed light on the future development of precision nanomedicine with improved delivery efficacy.
摘要:
蛋白质电晕效应长期以来一直被视为递送功效问题背后的邪恶来源。在这项研究中,这一概念受到了挑战,因为显示了蛋白质冠可以作为一种多功能的功能化方法来提高递送功效或减轻纳米细胞毒性。为此,引入耗尽的血清以创建携带功能不同的蛋白质电晕的纳米材料,称为PCylated纳米材料。证实了用耗尽的血清钝化有助于降低毒性和促炎反应。此外,可以利用相同的方法来增强纳米材料进行胞吞的能力以及它们作为NF-κB途径激动剂的潜力。晚期和早期血清产生的蛋白质电晕的相当稳定性表明,与纳米材料的无间相互作用,而不是结合强度不足,可能是丰富某些组件失败的背后。PCylation策略扩展到癌症患者来源的液体,创造了一套T1和T3阶段癌症特异性纳米疗法来延缓癌细胞的转移,而留下正常的内皮可忽略的影响。希望在此验证的新型PCylation方法可以阐明具有改善的递送功效的精密纳米医学的未来发展。