Cell-Penetrating Peptides TAT and 8R Enhance Virus-Like Particle Delivery With Distinct Tissue Targeting — TAT to Lungs, 8R to Brain

Both TAT and 8R CPPs significantly enhanced P22 VLP cellular uptake in vitro and tissue accumulation in vivo. At 24 hours post-injection, TAT-conjugated VLPs showed superior lung distribution and retention, while 8R-conjugated VLPs showed better brain accumulation. TAT was overall superior for cellular uptake and tissue accumulation.

In vitro and in vivo study: P22 VLP self-assembled particles prepared using a prokaryotic expression system with TAT- or 8R-conjugated mCherry on the capsid protein. Cellular uptake measured by fluorescence in vitro. Tissue distribution and retention assessed in animal models at multiple time points post-injection.

Targeted drug delivery remains a major challenge in medicine. This study demonstrates that different cell-penetrating peptides can direct the same nanoparticle platform to different tissues — TAT to lungs, 8R to brain — opening possibilities for tissue-specific drug delivery using a modular peptide-based targeting approach.

Virus-like particles are emerging as versatile delivery vehicles for drugs, vaccines, and imaging agents. Adding cell-penetrating peptides with tissue-specific homing properties could transform VLPs from passive carriers into actively targeted delivery systems, particularly valuable for lung diseases and neurological conditions.

Animal study with no human data. Tissue distribution was assessed using fluorescent reporter, not actual therapeutic cargo. Long-term retention and potential immunogenicity of VLP-CPP constructs not evaluated. The mechanism underlying differential tissue targeting of TAT vs 8R is not fully explained.