Engineering Modular Half-Antibody Conjugated Nanoparticles for Targeting CD44v6-Expressing Cancer Cells

摘要: Gastric cancer (GC) remains a major cause of death worldwide mainly because the late detection in advanced stage. Recently, we proposed CD44v6 as relevant marker for early GC, opening new avenues GC-targeted theranostics. Here, designed modular nanoscale system that selectively targets CD44v6-expressing GC cells by site-oriented conjugation new-engineered half-antibody fragment to maleimide-modified polystyrene nanoparticles (PNPs) via an efficient bioorthogonal thiol-Michael addition click chemistry. PNPs with optimal particle size (200 nm) crossing developed biomimetic CD44v6-associated stromal model were further modified heterobifunctional maleimide crosslinker and conjugated novel fragment, obtained chemical reduction full antibody, without affecting its bioactivity. Collectively, our results confirmed specific targeting ability CD44v6-PNPs (1.65-fold higher than controls), highlighting potential promising clinically tools diagnosis therapy GC. Additionally, rational design may be explored development several other nanotechnology-based disease-targeted approaches.