Photochemically triggered cytosolic drug delivery using pH-responsive hyaluronic acid nanoparticles for light-induced cancer therapy.

A photochemically triggered cytosolic drug delivery system based on combining tumor-targeting pH-responsive hyaluronic acid (HA) nanoparticles (PHANs) with anticancer therapeutics (doxorubicin; DOX) was successfully developed for light-induced cancer therapy. PHANs were prepared through the self-assembly of a photosensitizer (PS), chlorin e6, and a pH-responsive moiety, poly(diisopropylaminoethyl) aspartamide (PDIPASP),conjugated to HA. DOX encapsulating PHANs (DOX@PHANs) have a uniform spherical shape,a sub-100 nm size distribution and a negative surface charge. The pH-responsiveness of PHANs leads to their disassembly due to the protonation of PDIPASP, which triggers DOX release. Competitive cellular uptake and confocal microscopy studies revealed CD44 receptor-mediated endocytosis, endosomal escape capability and efficient drug targeting. Compared to treatment with free DOX or PHANs, the combined treatment with DOX@PHANs and spatiotemporally defined irradiation remarkably improved the anticancer efficacy both in vitro and in vivo studies. Therefore, this strategy shows promise for the photochemically triggered cytosolic drug delivery of therapeutic agents for light-induced cancer therapy.