Figure 5.
Schematic illustration of a multistage pH-responsive stepwise size reduction and charge-reversal polymeric nanocarrier. (A) negatively charged nanocarrier at neutral pH to enhance blood retention, (B) passive accumulation of larger size nanocarriers in the tumor via EPR effect, (C) the first-stage size reduction into smaller linear copolymers for tumor tissue deep penetration, (D) increased nanocarrier uptake by tumor cells mediated by concomitant R8NLS, (E) the second-stage size reduction into therapeutic drug for intracellular release in the endo/lysosomal compartment, (F) endo/lysosome escape and nuclear targeted delivery. Reproduced with permission from 189, copyright 2015 Wiley-VCH.