PHOTODYNAMIC THERAPY OF SOLID TUMORS USING NEAR-INFRARED EXCITABLE TITANIA COATED UPCONVERSION NANOPARTICLES

Abstract

CONVENTIONAL PHOTODYNAMIC THERAPY (PDT) IS LIMITED TO THE TREATMENT OF SUPERFICIAL AND FLAT LESIONS DUE TO THE LIMITED PENETRATION DEPTH OF VISIBLE LIGHT THAT EXCITES MOST PHOTOSENSITIZERS (PS). HERE, WE DEVELOPED A DEEP TISSUE PENETRATING NEAR-INFRARED (NIR) LIGHT EXCITABLE UPCONVERSION NANOPARTICLE (UCN), UNIFORMLY COATED WITH A PS OR PHOTOCATALYST TITANIUM DIOXIDE (TIO2-UCN). UCNS ACT AS A ?NANO-TRANSDUCER? CONVERTING NIR LIGHT TO ULTRAVIOLET (UV) LIGHT FOR INDIRECT ACTIVATION OF TIO2 INDUCING CANCER CELL KILL. STERIC STABILIZATION OF TIO2-UCNS WITH POLYETHYLENE GLYCOL (PEG) FURTHER IMPROVED ITS DISPERSION CHARACTERISTICS, ROS GENERATION AND SIGNIFICANTLY DELAYED TUMOR GROWTH FOLLOWING INTRATUMORAL ADMINISTRATION IN XENOGRAFT MOUSE TUMOR MODEL. FOR TARGETED DELIVERY TO EPITHELIAL GROWTH FACTOR RECEPTOR (EGFR) EXPRESSING ORAL CANCERS, THE NANOCONSTRUCT WERE FURTHER TAGGED WITH ANTI-EGFR AFFIBODIES. IN VIVO STUDIES FOLLOWING SYSTEMIC ADMINISTRATION REVEALED NO MAJOR SUB-ACUTE OR LONG