88850-36-6Relevant articles and documents
Tumor-targeting, pH-responsive, and stable unimolecular micelles as drug nanocarriers for targeted cancer therapy
Yang, Xiaoqiang,Grailer, Jamison J.,Pilla, Srikanth,Steeber, Douglas A.,Gong, Shaoqin
, p. 496 - 504 (2010)
A new type of multifunctional unimolecular micelle drug nanocarrier based on amphiphilic hyperbranched block copolymer for targeted cancer therapy was developed. The core of the unimolecular micelle was a hyperbranched aliphatic polyester, Boltorn H40. The inner hydrophobic layer was composed of random copolymer of poly(εcaprolactone) and poly(malic acid) (PMA-co-PCL) segments, while the outer hydrophilic shell was composed of poly(ethylene glycol) (PEG) segments. Active tumor-targeting ligands, i.e., folate (FA), were selectively conjugated to the distal ends of the PEG segments. An anticancer drug, i.e., doxorubicin. (DOX) molecules, was conjugated onto the PMA segments with pH-sensitive drug binding linkers for pH-triggered drug release. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) analysis showed that the unimolecular micelles were uniform with a mean hydrodynamic diameter around 25 nm. The drug loading content was determined to be 14.2%. The drug release profile, cell uptake and distribution, and cytotoxicity of the unimolecular micelles were evaluated in vitro. The folate-conjugated micelles can be internalized by the cancer cells via folate-receptormediated endocytosis; thus, they exhibited enhanced cell uptake and cytotoxicity. At pH 7.4, the physiological condition of bloodstream, DOX conjugated onto the unimolecular micelles exhibited excellent stability; however, once the micelles were internalized by the cancer cells, the pH-sensitive hydrazone linkages were cleavable by the intracellular acidic environment, which initially caused a rapid release of DOX. These findings indicate that these unique unimolecular micelles may offer a very promising approach, for targeted cancer therapy.
A convenient synthesis of novel bifunctional prochelators for coupling to bioactive peptides for radiometal labelling
Eisenwiener, Klaus-Peter,Powell, Pia,Maecke, Helmut R.
, p. 2133 - 2135 (2007/10/03)
New DOTA-based bifunctional prochelators, e.g., 1-(1-carboxy-3-carbotertbutoxypropyl)-4,7,10-(carbotertbutoxymethyl)-1,4,7,10 -tetraazacyclodode-cane (DOTAGA(tBu)4), (6d) for a broad application in the modification of biomolecules with metal ions were prepared. The five-step synthesis of 6d has an overall yield of about 20%. The coupling of 6d to a bioactive peptide on solid-phase was exemplified with use of a CCK-B (cholecystokinin) analogue. (C) 2000 Elsevier Science Ltd.
