Fig. 5.

Size-charge switching of NPs. I) “small-in-large” hybrid nanoparticle enhanced tumor penetration. The small QDs were encapsulated into larger GNPs and MMP-2 catalyzes the size reduction [161] (reproduced from Ref. [161] with permission). II) “Small-on-large” hybrid nanoparticle converted by low pH. PAMAM nanoparticles with Flu-label were conjugated onto larger PEG-b-PCL nanoparticles with RhB-label. When exposed to tumor acidity, the small nanoparticle is released, enhancing penetration [168] (reproduced from Ref. [168] with permission). III) Charge-transformable nanogel increases in vitro penetration in a 3D tumor spheroid model (Left), and charge-transformable nanogel enhanced in vivo penetration of DOX in xenografted hepatocellular carcinoma (Right) [175] (reproduced from Ref. [175] with permission). IV) Integration of size and charge transition into a single platform; size and charge transition of SNP exposed to pH 6.8, enhanced extravasation of SNP from tumor microvessels (Bottom left), and increased penetration of SNP from the tumor border to center (Bottom right) [164] (reproduced from Ref. [164] with permission).