pH-dependent solubility of particles incubated at pH 7.4 (PBS), pH 6.8 (PBS), or pH 5.0 (0.3 M acetate). (a) AcetalDextran-AuNPs (ADAs) were suspended in buffers (1.5 mg mL−1 by dry particle weight) and incubated at 37 °C under constant agitation for a total of 24 hours. Representative images shown. (b) Aliquots of ADAs were removed and measured for absorbance at 750 nm; results expressed as percent transmittance, average of three measurements ± standard deviation. (c,d) ADAs or AcetalDextran-AuNP-Micelles (ADAMs) were suspended in serum (0.04 mg mL−1 by Au, 1 mL) and incubated at 37 °C under constant agitation for a total of 24 hours. Particles were centrifuged at 16,000 × g for 10 minutes; separate tubes were prepared for each timepoint. (e) ADAMs were suspended in buffers (pH 7.4, purple lines; pH 5.0, blue lines) and hydrodynamic diameters were determined by dynamic light scattering. (f,g) Electron microscopy images of ADAMs suspended in buffer at pH 5.0 for either several seconds or 24 hours. Particles were diluted in water to reduce salt concentration and then dried on a grid for imaging. Scale bar = 100 nm.