Convenient Tuning of the Elasticity of Self-Assembled Nano-Sized Triterpenoids to Regulate Their Biological Activities

The impact of the mechanical properties of nanomedicines on their biological functions remains elusive due to the difficulty in tuning the elasticity of the vehicles without changing chemistry. Herein, we report the fabrication of elasticity-tunable self-assembled oleanolic acid (OA) nanoconstructs in an antiparallel zigzag manner and develop rigid nanoparticles (OA-NP) and flexible nanogels (OA-NG) as model systems to decipher the elasticity–biofunction relationship. OA-NG demonstrate less endocytosis and enhanced lysosome escape with deformation compared to OA-NP. Further in vitro and in vivo experiments show the active permeation of OA-NG into the interior of tumor with enhanced antitumor efficacy accompanied by decreased collagen production and eight- to tenfold immune cell infiltration. This study not only presents a facile and green strategy to develop flexible OA-NG for effective cancer treatment but also uncovers the crucial role of elasticity in regulating biological activity, which may provide reference for precise design of efficient nanomedicines.