Shibo Su # ,Xuegang Shen # ,Xinqi Shi, Xin Li, Jin Chen,Wei Yang,Mingxia Sun ,Yan-Dong Tang,Haiwei Wang,Shujie Wang,Xuehui Cai,Yu Lu,Tongqing An,Yongbo Yang,Fandan Meng

Front Vet Sci.2024 Sep 3:11:1460973.doi: 10.3389/fvets.2024.1460973. eCollection 2024.

Abstract

Virus-like particles (VLPs) are used as nanocontainers for targeted drug, protein, and vaccine delivery. The phage P22 VLP is an ideal macromolecule delivery vehicle, as it has a large exterior surface area, which facilitates multivalent genetic and chemical modifications for cell recognition and penetration. Arginine-rich cell-penetrating peptides (CPPs) can increase cargo transport efficiency  in vivo . However, studies on the tissue distribution and retention of P22 VLPs mediated by TAT and 8R are lacking. This study aimed to analyze the TAT and 8R effects on the P22 VLPs transport efficiency and tissue distribution both  in vitro  and  in vivo . We used a prokaryotic system to prepare P22 VLP self-assembled particles and expressed TAT-or 8R-conjugated mCherry on the VLP capsid protein as model cargoes and revealed that the level of P22 VLP-mCherry penetrating the cell membrane was low. However, both TAT and 8R significantly promoted the cellular uptake efficiency of P22 VLPs  in vitro , as well as enhanced the tissue accumulation and retention of P22 VLPs  in vivo . At 24 h postinjection, TAT enhanced the tissue distribution and retention in the lung, whereas 8R could be better accumulation in brain. Thus, TAT was superior in terms of cellular uptake and tissue accumulation in the P22 VLPs delivery system. Understanding CPP biocompatibility and tissue retention will expand their potential applications in macromolecular cargo delivery.

Keywords: 8R; P22 VLPs; TAT; biological nanoparticle; cellular uptake; tissue distribution.