This study demonstrates how nanoparticle rigidity affects cellular uptake and targeting in tumors, suggesting design principles for drug delivery systems.
Nanoparticle rigidity is a critical yet poorly understood regulator of nano-bio interactions, but decoupling rigidity from other properties (size, charge) remains challenging. Here, we synthesize ultrahigh-generation dye-cored polylysine dendritic dots (PDDs) with precisely tunable rigidity (Young's moduli: 0.93-1.90 GPa), enabling a systematic study of rigidity effects in megadalton dendrimers. These PDDs, produced at the gram scale with close size/charge but generation-dependent stiffness, reveal a striking mechanobiological trade-off: Stiffer PDDs exhibit enhanced cellular uptake, transcytosis, and deep penetration in three-dimensional (3D) tumor spheroids, while softer ones show prolonged blood circulation and superior tumor accumulation. This work deciphers rigidity's dual role in nano-bio interactions, presenting PDDs as a versatile model for mechanobiology studies and providing actionable design principles for next-generation drug delivery systems.
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Zhu et al. (2025) studied this question.
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