Size effect of mesoporous organosilica nanoparticles on tumor penetration and accumulation

The size effect of mesoporous organosilica nanoparticles (MONs) on tumor penetration and accumulation remains poorly understood, which strongly affects the tumor therapeutic efficacy. Herein, four different-sized thioether-bridged MONs (20, 40, 60, and 100 nm) are synthesized; all the MONs have a spherical morphology, excellent dispersity, similar surface charge, uniform mesopores (3.2-3.5 nm), and large surface areas (709-1353 m²·g^-1). Hematology and histopathology analyses demonstrate that the four MONs do not cause pathological changes in mice even at a dose of 20 mg kg^-1 for 30 d. The penetration depth of the MONs for multicellular spheroids (MCSs) decreases with increasing particle sizes, and the 20 nm MONs are uniformly distributed in the MCSs at a depth of 60 μm, while the larger MONs are mainly restricted to peripheral areas. In vivo experiments show that the 40 nm MONs possess the longest mean residence times, leading to their highest accumulation in blood and tumors. However, the 20 nm MONs reach the deepest penetration depth of 1230 μm for xenograft tumors. In contrast, the penetration depths of 40, 60, and 100 nm MONs are 783, 105, and 40 μm, respectively. Overall, this work provides an important guideline for the rational design of nanoplatforms for tumor treatment.