Nonimmunogenetic Viral Capsid Carrier with Cancer Targeting Activity.

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.