Multifunctional Core-shell Tecto Dendrimers Incorporated With Gold Nanoparticles For Targeted Dual Mode CT/MR Imaging Of Tumors

Due to the inherent weakness and limitation of single imaging modality,the combination of different imaging technologies is commonly used for the accurate diagnosis of tumor.As one of the most widely used imaging technology,computed tomography(CT)presents valuable anatomical structure and functional information with high spatial and density resolution,while magnetic resonance(MR)imaging has a highly sensitivity and excellent resolution for soft tissue.Therefore,the development of novel CT/MR dual-mode contrast nanoagents could integrate the advantage of each imaging modality and improve the sensitivity and accuracy of tumor diagnosis.Core-shell tecto dendrimers(CSTDs)are a kind of supermolecular assembly structures based on polyamide amine(PAMAM)dendrimers,and have attracted extensive attention in biomedical applications due to their excellent loading capability,easy surface modification and low toxicity.In this study,core-shell tecto dendrimers entrapped with gold nanoparticles(Au CSTDs)were constructed by using?-cyclodextrin(CD)-modified generation 5(G5)dendrimers entrapped with gold nanoparticles((Au⁰)₅₀-G5-CD)as a core and adamantine(Ad)-modified G3 PAMAM dendrimers(G3-Ad)as a shell through the supramolecular host-guest recognition,and then partially modified with RGD peptide and conjugated with Gd(III)chelator,and ending with the modification of 1,3-propane sultone(1,3-PS)to cover their leftover terminal amines to gain the targeted dual-mode CT/MR contrast agent RGD-Gd@Au CSTDs-PS.The experimental results showed that RGD-Gd@Au CSTDs-PS nanoprobes with an average diameter of 11.61 nm were successfully synthesized,and displayed good colloidal stability,antifouling performance,a significantly improved r₁relaxivity(9.41m M^-1s^-1)for MR imaging,and better X-ray attenuation characteristics and CT imaging effect than clinic used Omnipaque.In vitro experiments demonstrated that RGD-Gd@Au CSTDs-PS had good cytocompatibility and could specifically target breast cancer cells(4T1)overexpressing?v?3 integrin.Moreover,in vivo experiments proved that RGD-Gd@Au CSTDs-PS could effectively accumulate at the tumor site,significantly improve the CT and MR imaging effect of tumor site,and be cleared up24 h after injection.Therefore,the developed multifunctional nanoprobes may be effective and safe contrast agents for targeted CT/MR imaging of different types of cancer overexpressing?_v?₃ integrin.