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Doxorubicin loaded pH-responsive micelles capable of rapid intracellular drug release for potential tumor therapy.

Amphiphilic copolymers have been paid much attention for controlled drug release for many years due to their obvious advantages. In this study, an acid-triggered drug carrier system capable of rapid intracellular drug release is investigated for potential tumor therapy. The amphiphilic diblock copolymer poly(2-diisopropylaminoethyl methacrylate)-b-poly(2-aminoethyl methacrylate hydrochloride) (PDPA-b-PAMA) is prepared by atom transfer radical polymerization (ATRP). The molecular structure of the copolymer is confirmed by 1H NMR and gel permeation chromatography (GPC). The critical micelle concentration (CMC) value of the PDPA-b-PAMA is 0.005 mg/mL, which can ensure the thermodynamical stability of micelles even after significant dilution. The drug loading and encapsulation efficiencies of doxorubicin (DOX)-loaded micelles are 9.96% and 55.31%, respectively. Dynamic light scattering (DLS) and transmission electron microscope (TEM) show that the amphiphilic block copolymers self-assemble into spherical micelles with narrow polydispersity indexes (PDLs) at pH 7.4 and 6.8, but disassemble into random chain aggregations at pH 5.0. The DOX-loaded PDPA-b-PAMA shows obvious pH-responsive drug release profile when the pH value changes from 7.4 to 5.0, since it transforms from amphiphilicity to double hydrophilicity through the protonation of PDPA block (pK(a) - 6.2) in a relatively low pH condition, thus the loaded DOX can be rapidly released from the disassembling micelles. In addition, the micellar system also exhibits relatively low cytotoxicity and rapid drug release behaviour in tumor cells, which make it promising for tumor therapy.