Abstract
To promote the highly selective synergistic chemotherapy, the pH-ultra-sensitive dynamic methotrexate nano-prodrugs with detachable PEGylation were successfully prepared via facile method, and the synergistic nanodrugs could be further constructed through encapsulating Doxorubicin (DOX) following the self-assembly process. The nano-prodrugs exhibited the low critical micelle concentration (CMC), negative zeta potential and stability for 5 days in PBS and FBS at physiological pH (7.4) for stable blood circulation, DePEGylation and dynamic size change at tumoral extracellular pH (6.8) for improved tumor accumulation and cellular internalization, and efficiently synergistic drug release at tumoral intracellular pH (5.0) for enhanced tumor apoptosis and cytotoxicity. Moreover, in vivo experiment suggested that the synergistic nanodrugs could significantly improve tumor accumulation and restrain tumor growth while decreasing adverse effects. Therefore, the dynamic methotrexate nano-prodrugs with detachable PEGylation are easy to clinically transform for highly selective synergistic chemotherapy.
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