PH-responsive water soluble smart vesicles containing a bis(styryl)benzene derivative for two-photon microscopy imaging

We report self-assembled polymeric nanovesicles composed of 1,4-bis{4′-[N,N-bis(6′′-trimethylammoniumhexyl)amino]styryl} benzene tetrabromide (C1), poly[(ethylene oxide)-block-(sodium 2-acrylamido-2-methyl-1-propane sulfonate)] (E _m-A _n), and hexadecyltrimethylammonium bromide (C ₁₆). Transmission electron microscopy (TEM) micrographs confirm the vesicular bilayer structures and atomic force microscopy (AFM) images show that the C1/E _m-A _n/C ₁₆ complexes form spherical nanostructures with a particle size ranging from 40 to 80 nm. The encapsulation of C1 inside the nanovesicles enhances ∼2-fold the fluorescence quantum yield (η) and two-photon action cross-section (ηδ, where δ is the two-photon absorption cross-section), and allows internalization into the cells, as revealed by the bright two-photon microscopy (TPM) images of human cervical epithelioid carcinoma (HeLa) cells labeled with the nanovesicles. Moreover, nanovesicles containing a chemotherapeutic drug and a neutral molecule can also be prepared. Furthermore, the C1/vesicular complex is disassembled under acidic conditions, highlighting its potential as a pH-responsive smart nanocarrier for the intracellular drug delivery. These results suggest a new possibility of using nanovesicles as efficient two-photon probes for TPM imaging and possibly as nanocarriers for intracellular drug delivery.