A series of tetraphenylethylene-pyridine derivatives with multi-site substitutions for fluorescence nanoparticles: Structure-fluorescence relationship, pH-sensitivity, drug delivery and anti-tumor effect

The development of drug delivery systems with good biocompatibility, stability, fluorescence sensors and targeting capability is of great importance in biomedical research. In this work, we present the first systematic investigation of various site substitution effects on a series of fluorescent materials with aggregation-induced emission (AIE) characteristics. Thus, AIE active triphenylvinylbenzaldehyde (TPB) and triphenylvinylphenylpyridine (TPE-PY) derivatives with various aldehyde and pyridine positions were prepared via McMurry, Sonogashira and Suzuki reactions. As compared with TPB derivatives, TPE-PY derivatives showed significant changes in emission wavelength and intensity, displaying typical AIE behavior, longer wavelength emission, and pH-responsivity. Quantum chemical calculations also confirmed lower energy bandgaps (ΔE) of TPE-PY derivatives, in which TPE-PPY have the lowest ΔE (2.98 eV) due to extended conjugation effect. Considering the redshift and good fluorescence emission of TPE-4PY, DPT-4PY fluorescent organic nanoparticles (FONs) were prepared via physical encapsulation with amphiphilic DSPE-PEG2000, which exhibited excellent biocompatibility, low toxicity, and good potential for bioimaging applications. Furthermore, since TPE-PPY exhibited optimal fluorescence performance, a novel fluorescent monomer divinylbenzene-pyridin-acrylonitrile (DVBPA) with AIE characteristics was synthesized for the amphiphilic copolymer PEG-BPA from reversible addition-fragmentation chain-transfer (RAFT) polymerization, which would self-assemble to form nanoparticles about 100–200 nm in water solution. PEG-BPA FONs demonstrated superior fluorescence stability, biocompatibility, and cellular uptake, enabling their application as carriers of paclitaxel (PTX) to construct BPA-PTX FONs drug delivery system for anti-tumors effect. The drug-loaded nanoparticles exhibited high encapsulation efficiency, loading capacity, and significant A549 cells inhibition. This nano system is promising for applications in bioimaging, drug delivery, tumors microenvironment sensing, and anti-tumors therapy.