Abstract
To enhance the effectiveness and specificity of photodynamic therapy (PDT) in CD44-overexpressing cancers, the hyaluronic acid-b-poly (d,l-lactide-co-glycolide) copolymer (HA-b-PLGA) was synthesized, and potent photosensitizer protoporphyrin IX (PpIX) loaded polymeric micelles were prepared. The formulation organic solvent, polymer concentration, and feeding weight ratio of PpIX to polymer were optimized. PpIX-loaded HA-b-PLGA micelles (PpIX HA-PLGA micelles) were obtained with a drug loading rate of 2%, encapsulation efficiency of 43%, average diameter of 213 nm and zeta potential of −24 mV. The PpIX HA-PLGA micelles exhibited enhanced phototoxicity toward A549 cells. A cellular uptake study indicated that the micelles were internalized by CD44-mediated endocytosis. Exposure of A549 cell spheroids to HA-PLGA micelles showed deeper penetration and improved phototoxicity compared with nanoparticle and free drug analogues. PpIX HA-PLGA micelles have great potential for CD44-targeting delivery in PDT treatment.
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