Design of dual mode or multimode contrast agents or nanoplatforms with antifouling properties is crucial for improved cancer diagnosis since the antifouling materials are able to escape the clearance of the reticuloendothelial system with improved pharmacokinetics. Herein, we present the creation of zwitterionic gadolinium(III) (Gd(III))-complexed dendrimerentrapped gold nanoparticles (Au DEN) for enhanced dual mode computed tomography (CT)/magnetic resonance (MR) imaging of lung cancer metastasis. In the present work, poly(amidoamine) (PAMAM) dendrimers of generation 5 were partially decorated with carboxybetanie acrylamide (CBAA), 2-methacryloyloxyethyl phosphorylcholine (MPC), and 1,3-propane sultone (1,3-PS), respectively at different degrees, then used to entrap Au NPs within their interiors, and finally acetylated to cover their remaining amine termini. Through protein resistance, macrophage cellular uptake, and pharmacokinetics assays, we show that zwitterionic Au DEN modified with 1,3-PS exhibit the best antifouling property with the longest half-decay time (37.07 h) when compared to the CBAA-and MPC-modified Au DEN. Furthermore, with the optimized zwitterion type, we then prepared zwitterionic Gd(III)-loaded Au DEN modified with arginine-glycine-aspartic acid peptide for targeted dual mode CT/MR imaging of a lung cancer metastasis model. We disclose that the designed multifunctional Au DEN having an Au core size of 2.7 nm and a surface potential of 7.6 ± 0.9 mV display a good X-ray attenuation property, relatively high r 1 relaxivity (13.17 mM s −1 ), acceptable cytocompatibility, and targeting specificity to α v β 3 integrin-expressing cancer cells and enable effective dual mode CT/MR imaging of a lung cancer metastasis model in vivo. The developed multifunctional zwitterionfunctionalized Au DEN may be potentially adopted as an effective nanoprobe for enhanced dual-modal CT/MR imaging of other cancer types.

We report the synthesis and characterization of antifouling zwitterion carboxybetaine acrylamide (CBAA)-modified dendrimer-entrapped gold nanoparticles (Au DENPs) for enhanced CT imaging applications. The CBAA-modified nanodevice displays a better protein resistance property, less macrophage cellular uptake and liver accumulation, and longer blood half-delay time than the PEGylated counterpart material, thereby enabling enhanced blood pool, lymph node, and tumor CT imaging.

Chlorotoxin-conjugated multifunctional dendrimers labeled with radionuclide 131I were synthesized and utilized for targeted single photon emission computed tomography (SPECT) imaging and radiotherapy of cancer. In this study, generation five amine-terminated poly(amidoamine) dendrimers were used as a platform to be sequentially conjugated with polyethylene glycol (PEG), targeting agent chlorotoxin (CTX), and 3-(4'-hydroxyphenyl)propionic acid-OSu (HPAO). This was followed by acetylation of the remaining dendrimer terminal amines and radiolabeling with 131I to form the targeted theranostic dendrimeric nanoplatform. We show that the dendrimer platform possessing approximately 7.7 CTX and 21.1 HPAO moieties on each dendrimer displays excellent cytocompatibility in a given concentration range (0-20 μM) and can specifically target cancer cells overexpressing matrix metallopeptidase 2 (MMP2) due to the attached CTX. With the attached HPAO moiety having the phenol group, the dendrimer platform can be effectively labeled with radioactive 131I with good stability and high radiochemical purity. Importantly, the 131I labeling renders the dendrimer platform with an ability to be used for targeted SPECT imaging and radiotherapy of an MMP2-overexpressing glioma model in vivo. The developed radiolabeled multifunctional dendrimeric nanoplatform may hold great promise to be used for targeted theranostics of human gliomas.

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Novel theranostic nanocarriers exhibit a desirable potential to treat diseases based on their ability to achieve targeted therapy while allowing for real-time imaging of the disease site. Development of such theranostic platforms is still quite challenging. Herein, we present the construction of multifunctional dendrimer-based theranostic nanosystem to achieve cancer cell chemotherapy and computed tomography (CT) imaging with targeting specificity. Doxorubicin (DOX), a model anticancer drug, was first covalently linked onto the partially acetylated poly­(amidoamine) dendrimers of generation 5 (G5) prefunctionalized with folic acid (FA) through acid-sensitive cis-aconityl linkage to form G5·NHAc-FA-DOX conjugates, which were then entrapped with gold (Au) nanoparticles (NPs) to create dendrimer-entrapped Au NPs (Au DENPs). We demonstrate that the prepared DOX-Au DENPs possess an Au core size of 2.8 nm, have 9.0 DOX moieties conjugated onto each dendrimer, and are colloid stable under different conditions. The formed DOX-Au DENPs exhibit a pH-responsive release profile of DOX because of the cis-aconityl linkage, having a faster DOX release rate under a slightly acidic pH condition than under a physiological pH. Importantly, because of the coexistence of targeting ligand FA and Au core NPs as a CT imaging agent, the multifunctional DOX-loaded Au DENPs afford specific chemotherapy and CT imaging of FA receptor-overexpressing cancer cells. The constructed DOX-conjugated Au DENPs hold a promising potential to be utilized for simultaneous chemotherapy and CT imaging of various types of cancer cells.