基于 mRNA 的疫苗象征着治疗传染性和非传染性疾病的个性化医疗的新范式转变。然而，与目前批准的制剂相关的反应原性限制了它们在自身炎症性疾病（例如肿瘤治疗）中的适用性。在这项研究中，我们提出了一种递送系统，显示出受控的免疫原性和最小的非特异性炎症，允许选择性地将 mRNA 递送至淋巴结髓质区域内的抗原呈递细胞 (APC)。我们的平台通过优化隐形和靶向特性以及随后的调理过程，精确控制纳米颗粒在淋巴结内的运输。通过针对特定细胞，我们观察到了有效的适应性和体液免疫反应，这为预防性和治疗性抗肿瘤疫苗带来了希望。通过纳米颗粒分布的空间规划，我们可以促进强有力的免疫，从而改善和扩大mRNA疫苗的利用。这种创新方法标志着靶向纳米医学领域向前迈出了非凡的一步。版权所有 © 2024。由 Elsevier B.V. 出版。

mRNA-based vaccines symbolize a new paradigm shift in personalized medicine for the treatment of infectious and non-infectious diseases. However, the reactogenicity associated with the currently approved formulations limits their applicability in autoinflammatory disorders, such as tumour therapeutics. In this study, we present a delivery system showing controlled immunogenicity and minimal non-specific inflammation, allowing for selective delivery of mRNA to antigen presenting cells (APCs) within the medullary region of the lymph nodes. Our platform offers precise control over the trafficking of nanoparticles within the lymph nodes by optimizing stealth and targeting properties, as well as the subsequent opsonization process. By targeting specific cells, we observed a potent adaptive and humoral immune response, which holds promise for preventive and therapeutic anti-tumoral vaccines. Through spatial programming of nanoparticle distribution, we can promote robust immunization, thus improving and expanding the utilization of mRNA vaccines. This innovative approach signifies a remarkable step forward in the field of targeted nanomedicine.Copyright © 2024. Published by Elsevier B.V.