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Poly(amidoamine) (PAMAM) dendrimers functionalized with ligands that are designed to interact with biological receptors are important macromolecules for the elucidation and mediation of biological recognition processes. Specifically, carbohydrate functionalized dendrimers are useful synthetic multivalent systems for the study of multivalent protein–carbohydrate interactions. For example, lactose functionalized glycodendrimers can be used to discern the function of galectins, galactoside-binding proteins that are often over-expressed during cancer progression. In order to effectively interpret cancer cellular assays using glycodendrimers, however, their properties in the presence of cells must first be assessed. Macromolecules that are taken up by cells would be expected to have access to many different cell signaling pathways and modes of action that solely extracellular macromolecules cannot utilize. In addition, macromolecules that display cellular toxicity could not be used as drug delivery vehicles. Here, we report fundamental studies of cellular toxicity, viability, and uptake with four generations of lactose functionalized PAMAM dendrimers. In all cases, the dendrimers are readily taken up by the cells but do not display any significant cellular toxicity. The glycodendrimers also increase cellular apoptosis, suggesting that they may abrogate the antiapoptotic protections afforded by galectin- 3 to cancer cells. The results reported here indicate that appropriately functionalized PAMAM dendrimers can be used as nontoxic tools for the study and mediation of both extra and intracellular cancer processes. 

Abstract Fluorosurfactant-stabilized microfluidic droplets are widely used as pico- to nanoliter volume reactors in chemistry and biology. However, current surfactants cannot completely prevent inter-droplet transfer of small organic molecules encapsulated or produced inside the droplets. In addition, the microdroplets typically coalesce at temperatures higher than 80 °C. Therefore, the use of droplet-based platforms for ultrahigh-throughput combination drug screening and polymerase chain reaction (PCR)-based rare mutation detection has been limited. Here, we provide insights into designing surfactants that form robust microdroplets with improved stability and resistance to inter-droplet transfer. We used a panel of dendritic oligo-glycerol-based surfactants to demonstrate that a high degree of inter- and intramolecular hydrogen bonding, as well as the dendritic architecture, contribute to high droplet stability in PCR thermal cycling and minimize inter-droplet transfer of the water-soluble fluorescent dye sodium fluorescein salt and the drug doxycycline. 

Fluorescent linear dendronized polyols (LDPs) were prepared in two steps involving a ring-opening metathesis polymerization (ROMP) followed by acid-catalyzed deprotection. The resulting water-soluble fluorophores are compact in size (<6 nm) and show similar photostability compared to previously reported crosslinked dendronized polyols (CDPs) and significantly improved photostability compared to the free fluorophores. In contrast to the synthesis of CDPs, the production of LDPs requires less preparation time, synthetic effort, and significantly less Grubbs catalyst. The photophysical properties, including the photostability and emission wavelength of LDPs, can be further fine-tuned by incorporating different combinations of dendronized monomers and fluorophores. Interestingly, fluorescence resonance energy transfer (FRET) was observed when two different kinds of fluorophores were incorporated into the LDPs. This provides a new type of fluorophore with a large Stokes shift allowing fluorescence detection with reduced background overlap. Cytotoxicity and fluorescence imaging studies confirmed the biocompatibility of these LDPs, which make them potential candidates for biological applications.