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A novel hybrid hydrogel system based on N-(2-hydroxypropyl)methacrylamide copolymers was proposed. It consisted of the hydrophilic polymer backbone and a pair of oppositely charged peptide grafts. Two distinct pentaheptad peptides (CCE and CCK) were anticipated to create a dimerization motif and serve as physical cross-linkers. Consequently, the graft(More)
Telechelic water-soluble HPMA copolymers and HPMA copolymer-doxorubicin (DOX) conjugates have been synthesized by RAFT polymerization mediated by a new bifunctional chain transfer agent (CTA) that contains an enzymatically degradable oligopeptide sequence. Postpolymerization aminolysis followed by chain extension with a bis-maleimide resulted in linear high(More)
Improved treatments for prostate cancer are in great need to overcome lethal recurrence and metastasis. Targeting the tumorigenic cancer stem cells (CSCs) with self-renewal and differentiation capacity appears to be a promising strategy. Blockade of the hedgehog (Hh) signaling pathway, an important pathway involved in stem cell self-renewal, by cyclopamine(More)
A novel bone targeting, N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer based, prostaglandin E1 (PGE1) delivery system was designed, synthesized and characterized. PGE1 was bound to the polymer backbone via a spacer, composed of a cathepsin K sensitive tetrapeptide (Gly-Gly-Pro-Nle) and a self-eliminating 4-aminobenzyl alcohol structure. The HPMA(More)
Accurate assessment of human epidermal growth factor receptor (HER) 2 is essential for efficient selection of patients who may benefit from therapies targeting this surface receptor (e.g., trastuzumab). Intratumoral heterogeneity of HER2 expression may potentially contribute to inaccurate assessment of HER2 status. To clarify intratumoral heterogeneity of(More)
AIM To investigate the feasibility and efficacy of the combination of S-1 with gemcitabine followed by oral S-1 with concurrent radiotherapy (intensity modulated radiotherapy, IMRT) and maintenance therapy with S-1 for locally advanced pancreatic cancer. METHODS Subjects selected in the study were patients who had unresectable and locally advanced(More)
For rapid and effective clinical translation, polymer-based anticancer therapeutics need long circulating conjugates that produce a sustained concentration gradient between the vasculature and solid tumor. To this end, we designed second-generation backbone-degradable diblock N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer carriers and evaluated(More)
Graft copolymers were designed that self-assemble into hydrogels mediated by the interaction of coiled-coil peptide domains. A linear hydrophilic polymer of HPMA was chosen as the backbone, and coiled-coil forming peptides, covalently attached to the backbone, formed the grafts. Microrheology was used to evaluate the self-assembly of graft copolymers into(More)
To develop a biodegradable polymeric drug delivery system for the treatment of ovarian cancer with the capacity for non-invasive fate monitoring, we designed and synthesized N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-epirubicin (EPI) conjugates. The polymer backbone was labeled with acceptor fluorophore Cy5, while donor fluorophores (Cy3 or EPI)(More)
We studied the self-assembly of peptide-based ABA and CBC triblock-copolymers (obtained by bacterial expression) containing random coiled hydrophilic central B blocks flanked with helical A or C blocks. The A and C blocks were of different compositions with respect to the fraction of lysine residues which provided a higher pH sensitivity of the copolymer(More)