This section discusses the fundamental aspects of therapeutic cell-specific delivery addressing: (a) what to deliver (engineered therapeutic CD44v6shRNA delivery for in situ), (b) how to deliver (delivery strategies, in particular nonviral transferrin- (Tf-) coated PEG-PEI (Tf-PEG-PEI-nanoparticles) for in situ cell specific therapy), and (c) where to deliver (tumor-cell targets, in particular colon tumor cells for in situ cell-specific therapy). Here, TF is linked to colonic neoplasm.