A pH-responsive amphiphilic chitosan–pyranine core–shell nanoparticle for controlled drug delivery, imaging and intracellular pH measurement

Abstract

A pH-responsive multifunctional core–shell nanoparticle, named CHC–PY nanoparticle, was successfully synthesized through electrostatic interaction of a thin shell of fluorescent pyranine dye (PY) with amphiphilic carboxymethylhexanoyl chitosan (CHC) nanoparticles. Upon encapsulating an anticancer drug, camptothecin (CPT), the CHC–PY nanoparticles exhibited an excellent drug loading efficiency (>95%). The resulting CPT-loaded CHC–PY nanoparticles also exhibited efficient cell internalization and good pH-responsive behavior. After being internalized (via efficient endocytosis pathway), the presence of fluorescent PY shell showed a pH-dependent emission characteristic which allowed the internalized CHC–PY nanoparticles acting as an indicator to distinguish the acidic microenvironment of cancerous cells, compared with normal cells. The pH-sensitive PY shell also acted as a modulator to control the CPT release wherein a higher release rate was detected at lower pH value, which is essentially a potential therapeutic niche for anticancer purposes. This new type of CHC–PY core–shell nanoparticle provides multiple functionality, where a synergistic performance of nanotherapeutics, imaging and even diagnosis at a cellular resolution can be achieved simultaneously.