Self-assembling Dextran prodrug for redox- and pH-responsive co-delivery of therapeutics in cancer cells.
Self-assembling prodrug containing pH- and redox-responsive functional groups was prepared by covalent conjugation of Doxorubicin (Dox) and lipoic acid (LA) to a polyaldehyde Dextran (PAD). The resultant amphiphilic DoxPADLA forms, in a single step, hemocompatible vesicular systems able to respond to intracellular signals without using external crosslinking agents. Camptothecin (CPT) was encapsulated exploiting the hydrophobic interactions with the vesicle membrane, and release experiments, carried out in media mimicking the physiological and endolysosomial compartments, in the absence or presence of Glutathione, proved the ability of the system to modulate drug release in relation to the variation of pH and redox potential. Cytotoxicity assays and confocal experiments demonstrated the efficacy of the vesicle formulation in enhancing the synergistic anticancer effect of the delivered Dox and CPT and a rapid and significant internalization of the carrier in cancer cells.
['Curcio|Manuela|M|', 'Cirillo|Giuseppe|G|', 'Paolì|Alessandro|A|', 'Naimo|Giuseppina Daniela|GD|', 'Mauro|Loredana|L|', 'Amantea|Diana|D|', 'Leggio|Antonella|A|', 'Nicoletta|Fiore Pasquale|FP|', 'Iemma|Francesca|F|']
D000970:Antineoplastic Agents D002166:Camptothecin D002470:Cell Survival D003911:Dextrans D004317:Doxorubicin D016503:Drug Delivery Systems D065546:Drug Liberation D004705:Endocytosis D004951:Esterification D006801:Humans D006863:Hydrogen-Ion Concentration D061986:MCF-7 Cells D010084:Oxidation-Reduction D011355:Prodrugs D066244:Proton Magnetic Resonance Spectroscopy D017550:Spectroscopy, Fourier Transform Infrared
Self-assembling prodrugs Anticancer activity Dextran derivative Stimuli-responsive carrier