A Small Sugar Molecule with Huge Potential in Targeted Cancer Therapy.

The number of cancer-related diseases is still growing. Despite the availability of a large number of anticancer drugs, the ideal drug is still being sought that would be effective, selective, and overcome the effect of multidrug resistance. Therefore, researchers are still looking for ways to improve the properties of already-used chemotherapeutics.

Glycoconjugation of Quinoline Derivatives Using the C-6 Position in Sugars as a Strategy for Improving the Selectivity and Cytotoxicity of Functionalized Compounds.

Based on the Warburg effect and the increased demand for glucose by tumor cells, a targeted drug delivery strategy was developed. A series of new glycoconjugates with increased ability to interact with GLUT transporters, responsible for the transport of sugars to cancer cells, were synthesized. Glycoconjugation was performed using the C-6 position in the sugar unit, as the least involved in the formation of hydrogen bonds with various aminoacids residues of the transporter.

Shell-Sheddable Micelles Based on Poly(ethylene glycol)-hydrazone-poly[R,S]-3-hydroxybutyrate Copolymer Loaded with 8-Hydroxyquinoline Glycoconjugates as a Dual Tumor-Targeting Drug Delivery System.

The development of selective delivery of anticancer drugs into tumor tissues to avoid systemic toxicity is a crucial challenge in cancer therapy. In this context, we evaluated the efficacy of a combination of nanocarrier pH-sensitivity and glycoconjugation of encapsulated drugs, since both vectors take advantage of the tumor-specific Warburg effect. Herein, we synthesized biodegradable diblock copolymer, a poly(ethylene glycol)-hydrazone linkage-poly[R,S]-3-hydroxybutyrate, which could further self-assemble into micelles with a diameter of ~55 nm.

Synthesis and Preliminary Evaluation of the Cytotoxicity of Potential Metabolites of Quinoline Glycoconjugates.

The design of prodrugs is one of the important strategies for selective anti-cancer therapies. When designing prodrugs, attention is paid to the possibility of their targeting tumor-specific markers such as proteins responsible for glucose uptake. That is why glycoconjugation of biologically active compounds is a frequently used strategy.

Breaking down the barriers: siRNA delivery and endosome escape.

RNA interference (RNAi)-based technologies offer an attractive strategy for the sequence-specific silencing of disease-causing genes. The application of small interfering (si)RNAs as potential therapeutic agents requires safe and effective methods for their delivery to the cytoplasm of the target cells and tissues. Recent studies have shown significant progress in the development of targeting reagents that facilitate the recognition of and siRNA delivery to specific cell types.

Constituent-dependent liposome structure and organization.

We have used steady state and time-resolved fluorescence spectroscopy in concert with TEM to study organization and dynamics of molecules comprising liposomes, discoidal micelles, and spherical micelles. The lipid aggregates contained controlled amounts of lipids with headgroups modified with a thiol-terminated polyethylene glycol (thio-PEG lipids) and a small amount of 1-palmitoyl-2-(pyrene-1-yl)decanoyl-sn-glycero-3-phosphocholine (pyrene tethered DPPC), pyrene, or perylene as spectroscopic probes. The maximum diameter of the lipid aggregates was controlled by the polycarbonate filter pore size used in the extrusion process.

Interrogating interfacial organization in planar bilayer structures.

The field of biomimetic planar lipid membranes is finding increased importance as the need to devise sensing systems for biologically important species increases. We approach this area with an eye toward understanding how to interrogate local organization in these complex media. Our primary tools for this purpose are spectroscopy and electrochemistry, where imbedded reporter molecules serve as the information transducers.

Probing organization and communication at layered interfaces.

We have investigated the local organization intrinsic to a variety of interfacial structures, by both electrochemical and spectroscopic means. Our focus has been on the design and construction of biomimetic interfaces, where a lipid bilayer or a hybrid bilayer membrane can be bound to an interface. The goal of this work is ultimately to create an interface on a transducer surface that can support an enzyme in its active form.

Probing interfacial organization in surface monolayers using tethered pyrene. 2. Spectroscopy and motional freedom of the adsorbates.

We have studied the steady-state and time-resolved emission spectroscopy of the pyrene-containing monolayers reported in the previous article, where in this work we have bound the monolayers to SiO(x). We find that these monolayer structures are sensitive to the identity of the solvent overlayer, with the solvent playing a significant role in the organization of the surface-bound monolayers. We discuss our findings in the context of the known polarity dependence of the pyrene emission spectrum and find that the motional freedom of the chromophores varies with both the monolayer composition and the identity of the solvent overlayer.

Probing interfacial organization in surface monolayers using tethered pyrene. 1. Structural mediation of electron and proton access to adsorbates.

We have synthesized and characterized a family of self-assembled monolayers containing pyrene derivatives on gold and indium-doped tin oxide (ITO) substrates. The covalently bound pyrene functionalities serve as either spectroscopic or electrochemical probes of their immediate environment, and we explore their electrochemical response in this paper. When these compounds are the only constituents bound to the interfaces, the molecules enjoy significant structural freedom.