Chromophores that generate singlet oxygen (O) in water are essential to developing noninvasive disease treatments using photodynamic therapy (PDT). A facile approach for formation of stable colloidal nanoparticles of O photosensitizers, which exhibit aggregation enhanced O generation in water toward applications as PDT agents, is reported. Chromophore encryption within a fuchsonarene macrocyclic scaffold insulates the photosensitizer from aggregation induced deactivation pathways, enabling a higher chromophore density than typical O generating nanoparticles. Aggregation enhanced O generation in water is observed, and variation in molecular structure allows for regulation of the physical properties of the nanoparticles which ultimately affects the O generation. activity and the ability of the particles to pass through the cell membrane into the cytoplasm is demonstrated using confocal fluorescence microscopy with HeLa cells. Photosensitizer encryption in rigid macrocycles, such as fuchsonarenes, offers new prospects for the production of biocompatible nanoarchitectures for applications involving O generation.