Virus‐Inspired Deformable Mesoporous Nanocomposites for High Efficiency Drug Delivery

Abstract Mesoporous nanoparticles as a versatile platform for cancer theranostics have been widely used, but their cellular delivery efficiency is still far from satisfactory. Although deformability is emerging as an important parameter influencing cellular uptake enhancement, the facile synthesis of deformable mesoporous nanocomposite with adjustable mechanical property is challenging but meaningful for a deeper understanding of cellular uptake mechanisms and significantly improving cancer therapy. In this work, yolk–shell structured eccentric mesoporous organosilica (YEMO) nanocomposites with adjustable mechanical property are successfully prepared by an organosilane‐assisted anisotropic self‐assembly approach. The feasibility to precisely control the mechanical property of the YEMO by manipulating the structural parameters, the crosslinking degree of mesoporous framework, and the rotation rate of the reaction is demonstrated. The study of the fabrication mechanism and mechanical properties of YEMO are discussed in detail. The Young's modulus (E_Y) of YEMO can be adjusted from 2.4 to 65 MPa. Thereby, the continuous control of the cellular uptake from ≈15% to ≈80% under the same incubation time is achieved. To further prove the higher efficiency drug delivery of YEMO with soft characteristics, the higher toxicity of the “soft” YEMO loaded with the anticancer drug doxorubicin compared to the “stiff” one is demonstrated.