Mitochondria-targeted tri-triphenylphosphonium substituted meso-tetra(4-carboxyphenyl)porphyrin(TCPP) by conjugation with folic acid and graphene oxide for improved photodynamic therapy

Mitochondria are extensively researched as target sites to maximize photodynamic therapy (PDT) effects because they play crucial roles in metabolism. Here, a mitochondria targeting PDT agent, tri-triphenylphosphonium substituted meso-tetra(4-carboxyphenyl)porphyrin (TCPP-TPP) is prepared for the first time. Considering that many porphyrin derivatives are quick to aggregate, thereby reducing the PDT effect, our photosensitizer (PS) was loaded on a folic acid (FA) decorated graphene oxide (GO) nanosystem, called GF@TCPP-TPP, by electrostatic and pi-pi stacking or hydrophobic cooperative interactions, to improve the transportation of photosensitizers and enhance the therapeutic effect. Herein, we have performed a detailed study of photodynamic activity of GF@TCPP-TPP nanocomposites and evaluated their potential as a photosensitizer in PDT. An MU assay showed that GF@TCPP-TPP inhibited HeLa cells in a concentration-dependent manner under light (650 +/- 10 nm, 5 mW.cm(-2) and 10 min), and presented remarkably improved PDT efficiency (IC50 = 11.91 +/- 1.10 mu g.mL(-1) of equivalent TCPP-TPP) over free TCPP (IC50= 83.15 +/- 4.25 mu g.mL(-1)) after irradiation. Furthermore, our research indicated that Type I mechanisms (the generation of hydroxyl radicals) play a predominant role in the GF@TCPP-TPP induced PDT process. This coincides with the low singlet oxygen (O-1(2)) quantum yield (Phi(Delta)= 33.6%) in a DMF solution. Moreover, cell morphological changes after GF@TCPP-TPP PDT further demonstrated that GF@TCPP-TPP could induce damage and apoptotic cell death efficiently. In particular, precise delivery of photosensitizers to mitochondria was proven by organelle localization.