H2O2-Responsive amphiphilic polymer with aggregation-induced emission (AIE) for DOX delivery and tumor therapy

Schematic diagram of formation, transport and release DOX of TBP @DOX micelles. A TPE modified H 2 O 2 -responsive amphiphilic polymer, TBP , was designed and synthesized for the efficient loading, tracing and selectively triggered release of doxorubicin for tumor inhibition in vitro and in vivo . • A H 2 O 2 -responsive phenylborate amphiphilic polymer TBP showed the good ability to self-assemble into micelles with a strong fluorescence emission (AIE) and high encapsulation efficiency for DOX in aqueous solution. • In vitro release experiments indicated that TBP @DOX micelles showed high sensitivity and selectivity to H 2 O 2 with continuous release of DOX as well as good bio-compatibility and fluorescent tracing-ability. • In vivo experiment demonstrated that TBP @DOX could effectively accumulate in tumor tissues and inhibit growth of tumor. Stimuli-responsive drug delivery systems (DDSs) based on amphiphilic polymers have attracted much attention. In this study, we reported an innovative H 2 O 2 -responsive amphiphilic polymer ( TBP ), bearing a H 2 O 2 -sensitive phenylboronic ester, AIE fluorophore tetraphenylethene (TPE) hydrophobic, and polyethylene glycol hydrophilic (PEG) moieties. TBP could self-assemble into micelles with an encapsulation efficiency as high as 74.9% for doxorubicin (DOX) in aqueous solution. In the presence of H 2 O 2 , TBP micelles was decomposed by oxidation, hydrolysis and rearrangement, leading to almost 80% DOX release from TBP @DOX micelles. TBP and the corresponding degradation products were biocompatible, while TBP @DOX micelles only displayed obvious toxicity toward cancer cells. Drug delivery process was clearly monitored by confocal laser scanning microscopic (CLSM) and flow cytometry (FCM) analysis. Moreover, in vivo anticancer study showed that TBP @DOX micelles were accumulated in tumor region of nude mice and effectively inhibited tumor growth. The results suggested that the reported H 2 O 2 -responsive amphiphilic polymer displayed great potential in drug delivery and tumor therapy.