tempo and Neoplasms

Multicomponent reactions, especially the Ugi-four component reaction (U-4CR), provide powerful protocols to efficiently access compounds having potent biological and pharmacological effects. Thus, a diverse library of betulinic acid (BA), fusidic acid (FA), cholic acid (CA) conjugates with TEMPO (nitroxide) have been prepared using this approach, which also makes them applicable in electron paramagnetic resonance (EPR) spectroscopy. Moreover, convertible amide modified spin-labelled fusidic acid derivatives were selected for post-Ugi modification utilizing a wide range of reaction conditions which kept the paramagnetic center intact. The nitroxide labelled betulinic acid analogue

Topics: Antineoplastic Agents; Apoptosis; Betulinic Acid; Cell Line, Tumor; Cholic Acid; Cyclic N-Oxides; Electron Spin Resonance Spectroscopy; Fusidic Acid; Humans; Neoplasms; Pentacyclic Triterpenes; Small Molecule Libraries; Spin Labels; Steroids; Triterpenes

There is an urgent need for developing nanocarrier of excellent biocompatibility which can selectively release drugs at desired locations that can increase intratumoral drug concentration and reduce side effects. Herein, we developed a highly biocompatible nanocarrier made of oxidized starch in delivering doxorubicin (DOX) for enhanced anti-cancer therapy. The 30% oxidized starch can spontaneously self-assemble into 30-50 nm spherical nanoassemblies under physiological concentrations. DO30 nanoassemblies possessed negligible toxicity in several cell lines and ICR mice, in contrast to severe toxicity of synthetic polyacrylic acid (PAA), both of which are carboxyl-abundant polymers. The biocompatible DO30 was further decorated with cyclic RGD (Arg-Gly-Asp-Phe-Cys) peptides via PEG linker to target αvβ3 integrin overexpressed on HepG2 cells. RGD-PEG-DO30/DOX demonstrated an enhanced tumor-targeting ability and anti-cancer property in vitro and in vivo. In general, RGD-oxidized starch nanoassemblies showed a great potential as a new type of safe and effective nanocarrier for anti-cancer therapy.

Topics: Acrylic Resins; Animals; Antibiotics, Antineoplastic; Biocompatible Materials; Cyclic N-Oxides; Doxorubicin; Drug Carriers; Female; Hep G2 Cells; Humans; Integrin alphaVbeta3; Male; Mice; Mice, Inbred ICR; Nanoparticles; Neoplasms; Oligopeptides; Oxidation-Reduction; Starch; Tissue Distribution; Toxicity Tests; Xenograft Model Antitumor Assays

Nitroxides have great potential as magnetic resonance imaging (MRI) contrast agents for tumor detection. Polyacetylenes(PAs) containing 2,2,6,6-tetramethyl-piperidine oxyl (TEMPO) and poly(ethylene glycol) were synthesized via metathesis polymerization of the corresponding substituted acetylenes to be used for targeted bimodal MRI /optical imaging of tumors. The poly(ethylene glycol) in the polyacetylenes enables covalent conjugation of carboxyl fluorescein and folic acid (FA) with hydroxyl groups to develop targeted multifunctional organic radical contrast agents (ORCAs). In vitro studies confirm the excellent binding specificity and subsequent enhanced cellular internalization of the targeted ORCAs (PA-TEMPO-FI-FA) without cytotoxicity. In vivo T1-weighted MRI demonstrates the active tumor targeting ability of PA-TEMPO-FI-FA to generate specific contrast enhancement in mice bearing HeLa tumors. Moreover, longitudinal optical imaging displays high tumor accumulation after 1 h post-injection of PA-TEMPO-FI-FA. These results indicate that multifunctional ORCAs may provide a tumor-targeted delivery platform for further molecular imaging guided cancer therapy.

Topics: Animals; Contrast Media; Cyclic N-Oxides; Female; Folate Receptors, GPI-Anchored; HeLa Cells; Humans; Magnetic Resonance Imaging; Mice; Mice, Inbred BALB C; Mice, Nude; Molecular Imaging; Neoplasm Proteins; Neoplasms; Radiography