Folate-directed zinc (Ⅱ) phthalocyanine loaded polymeric micelles engineered to generate reactive oxygen species for efficacious photodynamic therapy of cancer

摘要

Targeted and effective drug transport is becoming an attractive option in cancer therapy since it can improve drug efficacy and reduce drugs' side effects in normal tissues. In addition to using specific surface ligand molecules, the selective drug delivery can be accomplished via enhanced permeability and retention effect. Therefore, in our studies, we entrapped zinc (II) phthalocyanine (ZnPc) - a second generation photosensitizer - in folate-functionalized micelles of the biocompatible, FDA-approved for biomedical application diblock copolymer methoxypoly(ethylene oxide)-b-poly(L-lactide) (mPEG-b-PLLA) and its derivative with folate (FA) attached to the end of PEG chain (FA-PEG-b-PLLA). Dynamic light scattering (DLS) measurements confirmed the micellar size to be 150 nm in diameter, a low polydispersity index, and good colloid stability of the studied nanocarriers, while atomic force microscopy (AFM) was used to study their morphology. The application potential of the resulting micelles was evaluated in cyto - and photocytotoxicity studies in conjunction with intracellular distribution and accumulation imaging of the photosensitizer delivered to ovarian carcinoma (SKOV-3) and metastatic melanoma (Me45) cell lines. Reactive oxygen species generation study was performed after photodynamic reaction, and cellular cytoskeleton reorganization was visualized after undergoing a photodynamic reaction. The results demonstrated that the functionalized polymeric micelles are promising nanocarriers for photodynamic therapy procedures and can be used in anticancer drug delivery.