Indocyanine green (ICG) is an FDA-approved photosensitizer dye used in clinical settings for optical diagnostics and near-infrared laser-based therapy. However, the rapid clearance and nonspecific vascular plasma binding issues impede ICG performance. Encapsulating ICG within a colloidal matrix is a potential approach to solving these problems, but thus far, there has been limited success. A new strategy, based on the nanoparticle assembly synthesis of stable, non-liposomal nanoparticle/polymer microcapsules, to encapsulate ICG is presented. Nanoparticle-assembled capsules (NACs) are prepared at room temperature, in aqueous solution, and at neutral pH by combining a polyallylamine solution, a phosphate solution, and an aqueous sol of silica nanoparticles; ICG-containing NACs with 0.6−1.0 μm diameter are prepared by adding an ICG solution before the nanoparticle sol. ICG loading is readily controlled with an attainable maximum loading of ∼23 wt %. There is negligible leakage from the capsules after 24 h at...