Aptamer-Pyropheophorbide a Conjugates with Tumor Spheroid Targeting and Penetration Abilities for Photodynamic Therapy.

Pyropheophorbide a (Pyro) is a widely used photosensitizer for photodynamic therapy (PDT). However, poor water solubility, aggregation-induced fluorescence quenching, and lack of selectivity to targeted cells seriously limit its application. In this work, we prepared aptamer-Pyro conjugates (APCs) by linking Pyro to hydrophilic nucleic acid aptamer to enhance its water solubility and endow it with protein tyrosine kinase 7 (PTK7) overexpressed tumor spheroid specific targeting and penetration abilities for photodynamic therapy. The molecular conjugate was successfully synthesized and dissolved well in an aqueous solution. The APCs showed strong near-infrared fluorescence in the aqueous solution and produced singlet oxygen both in the solution and cells under laser irradiation, indicating its generation of singlet oxygen during PDT was guaranteed. Owing to the cancer cell targeting ability of the aptamer, the APCs specifically bound with PTK7 overexpressed cancerous cells and showed fluorescence signal for tumor cell imaging and diagnosis. The APCs exhibited favorable enhanced phototoxicity to target tumor cells compared with control cells. More importantly, due to the small size of the molecular conjugate, the APCs efficiently penetrated into the interior of multicellular tumor spheroids (MCTS) and caused cell damage. All these results indicated that the robust aptamer-Pyro conjugate is a promising selective tumor-targeting and penetrable molecule for cancer photodynamic therapy.