Modular Self-Assembling Dendrimer Nanosystems for Magnetic Resonance and Multimodality Imaging of Tumors.

Bioimaging is a powerful tool for diagnosing tumors but remains limited in terms of sensitivity and specificity. Nanotechnology-based imaging probes able to accommodate abundant imaging units with different imaging modalities are particularly promising for overcoming these limitations. In addition, the nanosized imaging agents can specifically increase the contrast of tumors by exploiting the enhanced permeability and retention effect. A proof-of-concept study is performed on pancreatic cancer to demonstrate the use of modular amphiphilic dendrimer-based nanoprobes for magnetic resonance (MR) imaging (MRI) or MR/near-infrared fluorescence (NIRF) multimodality imaging. Specifically, the self-assembly of an amphiphilic dendrimer bearing multiple Gd3+ units at its terminals, generates a nanomicellar agent exhibiting favorable relaxivity for MRI with a good safety profile. MRI reveals an up to two-fold higher contrast enhancement in tumors than in normal muscle. Encapsulating the NIRF dye within the core of the nanoprobe yields an MR/NIRF bimodal imaging agent for tumor detection that is efficient both for MRI, at Gd3+ concentrations 1/10 the standard clinical dose, and for NIRF imaging, allowing over two-fold stronger fluorescence intensities. These self-assembling dendrimer nanosystems thus constitute effective probes for MRI and MR/NIRF multimodality imaging, offering a promising nanotechnology platform for elaborating multimodality imaging probes in biomedical applications.

Solid-Phase Synthesis of a Seventh-Generation Inverse Poly(amidoamine) Dendrimer: Importance of the Loading Ratio on the Resin.

Here, this study overcomes the current barriers to efficient solid-phase synthesis of high-generation dendrimers by decreasing the loading ratio on the resin. G7 inverse poly(amidoamine) dendrimer is now prepared, for the first time, through a solid-phase synthesis using only 50% of the available reactive sites and by choosing a large resin. This preparation takes only 15 d to afford highly pure product in 80% yield with precipitation being the only purification procedure used. The results clearly show the amount of the initial monomer loaded on the resin to be a vital factor for the ability to use solid-phase synthesis to produce large dendrimers. This finding also sets stage for the applications of solid-phase synthesis for the preparation of other macromolecules.

Concise solid-phase synthesis of inverse poly(amidoamine) dendrons using AB2 building blocks.

A concise solid-phase synthesis of inverse poly(amidoamine) dendrons was developed. Upon introduction of AB2-type monomers, each dendron generation was constructed via one reaction. G2 to G5 dendrons were constructed in a peptide synthesizer in 93%, 89%, 82%, and 78% yields, respectively, within 5 days.

Metallodendrimers and dendrimer nanocomposites.

Dendrimers are polymeric compounds with highly branched structures and functionally tunable peripheral groups. Because of their low polydispersity, high degree of molecular uniformity, and precisely controlled structure, dendrimers are excellent models for demonstrating a variety of biological activities. With the attachment of metals ions and/or metals, metallodendrimers or dendrimer nanocomposites, respectively, provide diverse characters for a variety of applications. Functionalization with additional moieties, such as targeted peptides or chromophores, yields metallodendrimers that can find powerful applications and exceed the capabilities of nondendritic molecules or small molecule analogs. This review introduces the background of metallodendrimers and dendrimer nanocomposites. Biomedical applications of metallodendrimers and dendrimer nanocomposites will be discussed, including biomimetic catalysts, imaging contrast agents (especially for MRI imaging), or biomedical sensors and therapeutic agents.