Although protein nanoparticles (PNPs) (e.g., viral capsids) capable of delivering a broad range of drug agents have shown distinctive advantages over synthetic nanomaterials, PNPs have an intrinsic drawback that hampers their clinical application, that is, potential immunogenicity. Here, a novel method for resolving the immunogenicity problem of PNPs, which is based on the genetic presentation of albumin‐binding peptides (ABPs) on the surface of PNP, is reported. ABPs are inserted into the surface of a viral capsid (hepatitis B virus capsid/HBVC) while preserving the native self‐assembly function of HBVC. The ABPs effectively gather human serum albumins around HBVC and significantly reduce both inflammatory response and immunoglobulin titer in live mice compared to ABP‐free HBVC. Furthermore, ABP‐conjugated HBVCs remain within tumors for a longer period than HBVCs conjugated to tumor cell receptor‐bindingpeptides, indicating that the ABPs are also capable of enhancing tumor‐targeting performance. Although applied to HBVC for proof of concept, this novel approach may provide a general platform for resolving immunogenicity and cancer‐targeting problems of PNPs, which enables the development of a variety of PNP‐based drug delivery carriers with high safety and efficacy.

中文翻译：

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具有癌症靶向活性的非免疫原性病毒衣壳载体

尽管能够递送多种药物的蛋白质纳米颗粒（PNP）（例如病毒衣壳）已显示出优于合成纳米材料的独特优势，但PNP具有阻碍其临床应用的固有缺点，即潜在的免疫原性。在此，报道了一种解决 PNP 免疫原性问题的新方法，该方法基于 PNP 表面白蛋白结合肽（ABP）的遗传呈现。ABP 被插入病毒衣壳（乙型肝炎病毒衣壳/HBVC）的表面，同时保留 HBVC 的天然自组装功能。与不含 ABP 的 HBVC 相比，ABP 有效地聚集 HBVC 周围的人血清白蛋白，并显着降低活小鼠的炎症反应和免疫球蛋白滴度。此外，与与肿瘤细胞受体结合肽缀合的 HBVC 相比，ABP 缀合的 HBVC 在肿瘤内保留的时间更长，表明 ABP 还能够增强肿瘤靶向性能。虽然应用于 HBVC 进行概念验证，但这种新方法可能为解决 PNP 的免疫原性和癌症靶向问题提供一个通用平台，从而能够开发各种具有高安全性和有效性的基于 PNP 的药物输送载体。