Catechol-boronate ester engineered AIE nanocarriers with pH-responsive drug release for fluorescence-guided cancer theranostics

Developing efficient drug delivery systems (DDS) is crucial for cancer therapy. Herein, we report the construction of a pH-responsive DDS using an aggregation-induced emission (AIE)-active carrier (termed as TPA-CHTAD-PEG-DA), which is engineered by integrating dopamine (DA) on the side chains of AIE-active TPA-CHTAD-PEG copolymer. TPA-CHTAD-PEG-DA pendant with DA can form dynamic catechol-boronate ester with anti-cancer drug bortezomib (BTZ) to form the aimed DDS (TCP-DA-BTZ). We demonstrated that TCP-DA-BTZ can self-assemble into nanoparticles with high water dispersibility, intense fluorescence and high drug-loading capacity (15.5 %). The DDS showed a significant pH-responsive drug release profile, with minimal leakage under physiological pH (26.3 % at pH 7.4) but rapid drug release under acidic conditions (50 % at pH 5.0). In vitro experiments suggested TPA-CHTAD-PEG could be efficiently internalized by cancer cells and exhibited neglected cytotoxicity, while TCP-DA-BTZ exerted considerable or even stronger cell killing ability towards MDA-MB-231 cells compared with free BTZ. Considering the above aspects, such as high drug loading capacity, pH-responsive drug release, and intrinsic imaging capabilities, the AIE-active pH-responsive DDS developed in this work is expected to overcome limitations (e.g., off-target toxicity and inadequate spatiotemporal control) of conventional chemotherapy, holding great potential for fluorescence-guided cancer theranostics.