Two-photon photodynamic therapy based on FRET using tumor-cell targeted riboflavin conjugated graphene quantum dot

The photodynamic therapy (PDT) is considered as a noninvasive and photo-controlled treatment for various cancers. However, its potential is not fully developed as current clinically approved photosensitizers (PSs) mainly absorb the light in the UV-visible region (less than 700 nm), where the depth of penetration is inadequate for reaching tumor cells under deeper tissue layers. Furthermore, the lack of specific accumulation capability of the conventional PSs in the tumor cells may cause serious toxicity and low treatment efficiency. To address these problems, riboflavin (Rf) conjugated and amine-functionalized nitrogen-doped graphene quantum dots (am-N-GQD) are herein proposed. Rf functions as both photosensitizer and targeting ligand by indirect excitation through intra-particle fluorescence resonance energy transfer (FRET) via two-photon (TP) excited am-N-GQD, to enhance the treatment depth, and further am-N-GQD-Rf accumulation in cancer cells using Rf transporter family (RFVTs) and Rf carrier proteins (RCPs). The one-photon (OP) and two-photon(TP)-PDT effect and cellular internalization ability of the am-N-GQD-Rf were investigated in vitro in different cancel cell lines. Besides the excellent cellular uptake as well TP-PDT capability, the superior biocompatibility of am-N-GQD-Rf in vitro makes it promising candidate in PDT.