Abstract:
Porphyrin is known to enable the photodynamic effect during cancer drug delivery and molecular imaging. However, its hydrophobicity and tendency to aggregate in an aqueous medium create a significant hurdle for its use as an anticancer drug. Loading porphyrin onto biocompatible delivery vehicles can enhance its efficacy. This can be achieved by using gas-filled microbubbles that can be administered intravenously. This study aimed at developing near-infrared (NIR)-active porphyrin-loaded lipid microbubbles with anticancer activity enhanced by sonodynamic and photodynamic effects. The porphyrin-loaded microbubbles were studied for their cell toxicity, cellular uptake of porphyrin, and effect on cellular three-dimensional (3D) invasion of breast cancer cells (MDA-MB-231) in cellulo. Toxicity studies in zebrafish larvae (Danio rerio) in the presence and absence of photodynamic and sonodynamic therapy were also conducted. The results suggest that with a higher concentration of porphyrin loaded on microbubbles, the porphyrin-loaded microbubbles display a higher therapeutic effect facilitated by photodynamic and sonodynamic therapy, which results in enhanced cellular uptake and cellular toxicity. A lower concentration of loaded porphyrin microbubbles exhibits high cellular viability and good fluorescence intensity in the NIR region, which can be exploited for bioimaging applications.