Polystyrene@poly(ar-vinylbenzyl)trimethylammonium-co-acrylic acid core/shell pH-responsive nanoparticles for active targeting and imaging of cancer cell based on aggregation induced emission

Doubly charged pH-responsive core/shell hydrogel nanoparticles with green fluorescence were prepared and were shown to be viable bioprobes for active targeting tumor tissue and imaging of cancer cells. Via emulsionfree copolymerization hydrogel nanoparticles as VANPs were prepared, the core of which was polystyrene (Ps) and the shell was comprised of strongly positive electrolyte (ar-vinylbenzyl)trimethylammonium (VBTAC) with weak negative electrolyte acrylic acid (AA). Through conventional amidation, the shell was conjugated with cell-specific folic acid (FA), denoted as VANPs-FA. Then, negatively charged sulfonated 9,10-distyrylanthracene derivatives (SDSA) based on aggregation induced emission (AIE), was binding tightly to positively charged VBTAC of VANPs-FA shell. The prepared double charged fluorescent core/shell hydrogel nanoparticles abbreviated as VANPs-FS, showed excitation/emission wavelengths at ~420/528 nm. Dynamic light scattering (DLS) measurements were performed to determine the size and surficial zeta potential of VANPs-FS. Under proper ratio of VBTAC to AA, the VANPs-FS was stable (~ 64.63 nm, -20.2 mV) at high pH (> 7), started to aggregate (~ 683.0 nm, -3.2 mV) at pH around 6, and can redispers at low pH (< 5). The MTT analysis proved that VANPs-FS had good biocompatibility and low cytotoxicity. The targeting effectiveness of VANPs-FS was confirmed by confocal laser scanning microscopy (CLSM). Graphical abstract Detailed synthetic route of VANPs-FS (top) and schematic cancer tumor-target aggregation of pH-sensitive VANPs-FS with enhanced retention and rapid cancer cell imaging (bottom).