Investigating the optimal size of anticancer nanomedicine

TLDR

Nanomedicines offer new solutions for cancer diagnosis and therapy, yet FDA‑approved formulations have only modestly extended progression‑free interval and overall survival. The study aims to develop next‑generation nanomedicines by investigating how particle size influences biological interactions to establish optimization criteria for superior anticancer activity. The authors evaluated size‑dependent biological profiles of three monodisperse drug‑silica nanoconjugates (20, 50, and 200 nm) using experiments and mathematical modeling to pinpoint the optimal size for drug delivery. The 50‑nm nanoconjugate exhibited the greatest tumor retention and, consequently, the highest efficacy against primary and metastatic tumors in vivo.

Abstract

Nanomedicines (NMs) offer new solutions for cancer diagnosis and therapy. However, extension of progression-free interval and overall survival time achieved by Food and Drug Administration-approved NMs remain modest. To develop next generation NMs to achieve superior anticancer activities, it is crucial to investigate and understand the correlation between the physicochemical properties of NMs (particle size in particular) and their interactions with biological systems to establish criteria for NM optimization. Here, we systematically evaluated the size-dependent biological profiles of three monodisperse drug-silica nanoconjugates (NCs; 20, 50, and 200 nm) through both experiments and mathematical modeling and aimed to identify the optimal size for the most effective anticancer drug delivery. Among the three NCs investigated, the 50-nm NC shows the highest tumor tissue retention integrated over time, which is the collective outcome of deep tumor tissue penetration and efficient cancer cell internalization as well as slow tumor clearance, and thus, the highest efficacy against both primary and metastatic tumors in vivo.