Efficient delivery of chlorin e6 into ovarian cancer cells with octalysine conjugated superparamagnetic iron oxide nanoparticles for effective photodynamic therapy

Abstract

In cancer treatment, efficient delivery of active anticancer drugs into cancer cells is highly desirable for maximizing therapeutic effects and alleviating side effects. In this work, a nanocarrier consisting of an Fe₃O₄ core, a polyglycerol coating, and an octalysine functionality (SPION-PG-Lys₈) has been designed, synthesized and used to deliver a photosensitizer, chlorin e6 (Ce6), into cancer cells for photodynamic therapy (PDT) of cancer cells. SPION-PG-Lys₈ is colloidally stable in various aqueous solutions, showing a high positive zeta potential of 47.2 ± 6.9 mV in pure water. In vitro characterization reveals that SPION-PG-Lys₈ is efficiently taken up by SKOV3 ovarian cancer cells, exhibiting low cytotoxicity, and suppressed autophagy compared to bare SPIONs. Negatively charged Ce6 is thus loaded on the SPION-PG-Lys₈ through electrostatic attraction to yield a SPION-PG-Lys₈/Ce6 nanocomplex with a positive zeta potential of 22.4 ± 4.3 mV. SPION-PG-Lys₈/Ce6 is more easily taken up by the cells than free Ce6, and surprisingly, the internalized SPION-PG-Lys₈/Ce6 is found to be enriched in the mitochondria. SPION-PG-Lys₈/Ce6 exhibits almost no cytotoxicity under dark conditions, but strong photocytotoxicity due to the light-triggered production of reactive oxygen species (ROS) destroying the mitochondria. Taken together, our results highlight the great potential of SPION-PG-Lys₈ as an efficient carrier of Ce6 for photodynamic cancer therapy.