NIR and UV-responsive degradable hyaluronic acid nanogels for CD44-targeted and remotely triggered intracellular doxorubicin delivery.

Hyaluronic acid (HA) is an endogenous polysaccharide that shows intrinsic targetability to CD44+ cancer cells. Here, we developed NIR and UV-responsive degradable nanogels from hyaluronic acid-g-7-N,N-diethylamino-4-hydroxymethylcoumarin (HA-CM) for CD44 targeted and remotely controlled intracellular doxorubicin (DOX) delivery. Nanometer-sized HA-CM nanogels could readily load DOX, and both NIR and UV irradiation could significantly enhance DOX release from the nanogels, resulting from light-triggered cleavage of urethane bonds that connect CM to HA. MTT assays showed that DOX-loaded HA-CM nanogels combined with NIR irradiation induced much higher antitumor activity to MCF-7 cells (CD44+) than to U-87MG cells (CD44-) and free HA pretreated MCF-7 cells. CLSM observations confirmed that DOX-loaded HA-CM nanogels were internalized by CD44+ cells via receptor mediated endocytosis mechanism, and intracellular DOX release was triggered by NIR. These HA-CM nanogels with easy preparation, CD44 targetability and photo-controlled intracellular drug release are interesting for cancer chemotherapy.