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pH-Responsive Nanophotosensitizer for an Enhanced Photodynamic Therapy of Colorectal Cancer Overexpressing EGFR.
Molecular Pharmaceutics 2018 April 3
Photodynamic therapy (PDT) has been shown to kill cancer cells and improve survival and quality of life in cancer patients, and numerous new approaches have been considered for maximizing the efficacy of PDT. In this study, a new multifunctional nanophotosensitizer Ce6/GE11-(pH) micelle was developed to target epidermal growth factor receptor (EGFR) overexpressing colorectal cancer (CRC) cells. This nanophotosensitizer was synthesized using a micelle comprising pH-responsive copolymers (PEGMA-PDPA), biodegradable copolymers (mPEG-PCL), and maleimide-modified biodegradable copolymers (Mal-PEG-PCL) to entrap the potential hydrophobic photosensitizer chlorin e6 (Ce6) and to present EGFR-targeting peptides (GE11) on its surface. In the presence of Ce6/GE11-(pH) micelles, Ce6 uptake by EGFR-overexpressing CRC cells significantly increased due to GE11 specificity. Moreover, Ce6 was released from Ce6/GE11-(pH) micelles in tumor environments, leading to improved elimination of cancer cells in PDT. These results indicate enhanced efficacy of PDT using Ce6/GE11-(pH) micelle, which is a powerful nanophotosensitizer with high potential for application to future PDT for CRC.
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