Towards the Synthesis of New Tumor Targeting Photosensitizers for Photodynamic Therapy and Imaging Applications

The synthesis of three complexes, which bear tumor-targeting peptide and which are suitable for imaging applications might act at the same time, is reported. Their structure contain a PS (a porphyrin or a fulleropyrrolidine derivative), a [1,4,7]-triazacyclononane (TACN) chelator suitable for coordination, and a bombesin BN[7-14] as a targeting peptide. Overall, this work paves the way for the preparation of theranostic complexes although the yields will need to be seriously improved and the synthetic process optimized. Targeting peptides are very promising molecules to increase tumor selectivity of anticancer drugs. Herein, we report the synthesis of three complexes, which might act at the same time as photosensitizers (PSs) for cancer photodynamic therapy (PDT), as delivery systems of Re(I)/99mTc(I) fragments into tumor cells as well as targeting agents for prostate cancer cells. To this aim, we designed a structure containing a PS such as a water soluble +3-charged tris-methylpyridinium porphyrin or a fulleropyrrolidine derivative, a [1,4,7]-triazacyclononane (TACN) chelator suitable for coordination, and a bombesin BN[7-14] as a targeting peptide. Their syntheses were performed using two different approaches: the first one was based on a Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC, “click reaction”) in solution, that led to compound 1, and the second one based on coupling reactions on the solid phase, that led to compounds 2 and 3. We could successfully prepare molecules bearing tumor-targeting PSs and which are suitable for imaging applications. Overall, this work paves the way for the synthesis of theranostic complexes although the yields will need to be seriously improved and the synthetic process optimized.