A series of tetraphenylene-acetonitrile AIE compounds with D-A-D′ structure for drugs delivery systems of paclitaxel: Synthesis, structure-activity relationship and anti-tumors effect

Abstract

Aggregation-induced emission (AIE) materials are attracting great attention in biomedical fields such as sensors, bioimaging, and cancer treatment, et al. due to their strong fluorescence emission in the aggregated state. In this contribution, a series of tetraphenylene-acetonitrile AIE compounds with D-A-D′ structures were synthesized by Suzuki coupling reaction and Knoevenagel condensation, and their relationship of chemical structure and fluorescence properties was investigated in detail, among which TPPA compound was selected as the monomer owing to the longest emission wavelength at about 530 nm with low energy band gap ΔE 3.09 eV of neutral TPPA and 1.43 eV of protonated TPPA. Novel amphiphilic AIE PEG-TA copolymers were prepared by RAFT polymerization of TPPA and PEGMA with about 1.44×104 Mw and narrow PDI, and the molar ratio of TPPA in the PEG-TA1 and PEG-TA2 copolymers was about 23.4 % and 29.6 %. The as-prepared PEG-TA copolymers would self-assembled in aqueous solution to form core-shell structures with a diameter of 150–200 nm, and their emission wavelength could reversibly convert from 545 nm to 650 nm with excellent pH sensitivity. The CLSM images showed that the PEG-TA FONs and PTX drugs-loaded PTX-TA FONs could be endocytosed by cells and mainly enriched in the cytoplasm, and CCK-8 results showed that the PEG-TA FONs had excellent biocompatibility but PTX-TA FONs had high inhibition ratio for A549 cells, moreover, the flow cytometry also showed that PTX-TA FONs could result in the apoptosis of A549 cells with some extent anti-tumor effect.