MicroRNA-Responsive Drug Release System for Selective Fluorescence Imaging and Photodynamic Therapy In Vivo

Photodynamic therapy (PDT) is a noninvasive strategy to treat diseases by light-triggered activation of a photosensitizer (PS). One aim of the recent researches on PDT is to overcome the limitation of conventional PDT by improving selective activation of PS on targeted region. Here, a microRNA (miRNA)-responsive drug activation system is developed which focuses on the role of endogenous miRNA as an internal cancer specific stimulus for initiating drug release in cancer treatment. The present system consists of PS chlorin e6 (Ce6) conjugated to peptide nucleic acid (PNA) having complementary sequence to cancer specific miRNA and dextran coated reduced graphene oxide nanocolloid (Dex-RGON). In the presence of oncogenic miR-21 in cancer cells, Ce6-PNA drug gets hybridized with miR-21, resulting in the release of Ce6-PNA from Dex-RGON and subsequent recovery of Ce6 fluorescence and activation of Ce6 as a photosensitizer under near IR irradiation. It is demonstrated that the Ce6-PNA/Dex-RGON complex shows sequence-specific fluorescence in response to miR-21 and selective cytotoxic effect for tumor growth inhibition. The present study will pave a new way for utilizing PDT in cancer treatment with tightly regulated activation of a photosensitizer by oncogenic miRNA as an internal stimulus to reduce potential risk associated with conventional PDT.