Despite great efforts having been devoted to the design of multimodal imaging probe, almost all design principles of nanotheranostic agents subordinate to simple assemblies of building blocks, resulting in complex preparation process and discounted ability, that is, 1 + 1 < 2. In this report, a novel design strategy, marriage of structure design and composition design that can maximize imaging ability of each building block, ultimately achieving 1 + 1 ≥ 2, has been established. Moreover, a high-efficient ultrasound (US) & MR & CT trimodal contrast agent acts as model to instantiate this design strategy, wherein nanoparticles-induced nonlinear scattering and rattle-type structure-induced double scattering enhancing US imaging, and uniform distribution of Mn(2+) paramagentic centers and "core-satellite" structure of Au atoms favoring enhanced MR imaging and CT imaging, respectively have been validated, achieving optimization of structure design. Importantly, the selected components, silica, Au and MnO are endowed with excellent biocompatibility, displaying the marriage strategy of composition design with aforementioned structure optimization. In in vivo evaluations, such a biocompatible trimodal probe is demonstrated of excellent performance in intensifying CT, MR and US imaging in vivo, especially after positively charged modification by PEI promoting more probes retained in tumor. More importantly, as a universal design strategy, the involved principles in constructing such a US&MR&CT trimodal imaging probe promise great potentials in guiding designs of other materials-based multimodal imaging probe.
Keywords: composition & structure marriage; core−satellite; double scattering; enhanced nonlinear scattering; ultrasound & MR & CT trimodal imaging probe; uniform distribution.