Multifunctional Core–Shell Tecto Dendrimers Incorporated with Gold Nanoparticles for Targeted Dual Mode CT/MR Imaging of Tumors
Renna Liu, Honghua Guo, Zhijun Ouyang, Yu Fan, Xueyan Cao, Jindong Xia, Xiangyang Shi, Rui Guo
Abstract
Development of multifunctional nanoprobes with an excellent imaging performance for precision tumor imaging still remains a great challenge. Here, we report the creation of multifunctional core–shell tecto dendrimers (CSTDs) incorporated with gold nanoparticles (Au NPs) as a platform for dual-mode computed tomography (CT)/magnetic resonance (MR) imaging of tumors. In this work, β-cyclodextrin (CD)-modified generation 5 poly(amidoamine) (PAMAM) dendrimers were synthesized and entrapped with Au NPs as the core. Then, adamantine (Ad)-modified generation 3 PAMAM dendrimers acted as a shell to form Au NP-entrapped CSTDs (for short, Au CSTDs) through supramolecular host–guest recognition between CD and Ad. The formed Au CSTDs were sequentially modified with Arg-Gly-Asp (RGD) peptide through a spacer of polyethylene glycol (PEG), Gd chelator, and 1,3-propane sultone, followed by chelating Gd (III) ions. The synthesized multifunctional Au CSTDs with a mean size of 11.61 nm possess good colloidal stability, high X-ray attenuation property and high r1 relaxivity (9.414 mM–1 s–1), good antifouling property, and desired cytocompatibility. Due to the RGD-mediated targeting specificity to αvβ3 integrin-overexpressing cancer cells, the multifunctional Au CSTDs enable targeted CT/MR dual mode imaging of a breast cancer model in vivo and can be cleared out of body through metabolization pathway with good biosafety profile. The developed multifunctional CSTDs may be applied as an effective CT/MR dual mode imaging probe for accurate diagnosis of various αvβ3 integrin-overexpressing cancer types.