Chemical design and characterization of the MNPs with pH-sensitive charge reversion for controlled intracellular aggregation. (A) Synthesis process of various MNPs in the aggregation system. (a) Negatively charged MNPs with particle size of 5 nm (M5) and 20 nm (M20), (b) synthesis of charge reversible MNPs (M20@DPA/HA) with oxidized hyaluronic acid (HA-CHO) coating and hydrazone linkage. (B) Thermogravimetric (TGA) curve of various MNPs. (C) Z-average size, zeta potential and optical photo (D) of M5, M20, M20@DPA and M20@DPA/HA, respectively. (E) Size change of M5&20 and M20&20 with different pH. (F) Morphology of various MNPs by TEM observation at pH 7.4 (a-c) and 5.5 (d and e). When HA was drop off in the extracellular acidic condition, positively charged M20@DPA would aggregate with negatively charged M5 or M20 via electrostatic interactions to form A-M5&20 or A-M20&20. (G) Temperature change curves of individual MNPs and their aggregations under alternating magnetic field (AMF) (2 mg Fe/mL, 15 KA/m, 300 kHz). (H) Infrared thermal imaging of MNPs (2 mg/mL) under AMF for 120 s. (I) T2-weighted images of different MNPs and aggregations dispersed in 1% agarose gel at indicated concentrations under a 7.0 T magnetic field. The scale bars are 20 and 50 nm, respectively.