Abstract

Photodynamic therapy (PDT), as a very promising treatment modality for cancer, has several advantages over conventional therapies because of its noninvasive nature, the fast healing process, and none ionizing radiation. However, the clinical efficacy of PDT needs to be further improved, and there are many obstacles still existed, such as the limited tumor selectivity of the clinically used photosensitizers, severe tumor hypoxia which has been associated with resistance to therapy, tumor recurrence and distal metastasis after oxygen consumption by PDT. In addition, single photodynamic therapy modality can not completely eliminate the tumor cells. To solve the above mentioned problems, our group has developed a smart nanosystem for tumor micro-enviroment triggered programmable in demand photodynamic therapy, aggregation induced photothermal therapy and hypoxia-activated chemotherapy. This nanosystem is composed of HCC cell specific targeting aptamers (TLS11a), monodispersed gold nanoparticle (GNP), photosensitizer (Ce6), and hypoxia activatable prodrug (AQ4N). In normal physiological conditions, the fluorescence and ROS generation ability of Ce6 are quenched by GNPs via resonance energy transfer (RET); but in cancerous cells, the fluorescence and the ROS generation of Ce6 could be recovered by cleavage of Au-S bond through high level of intracellular GSH for real-time imaging and in demand PDT. Meanwhile, the prodrug AQ4N release could be triggered by acid-cleavage of coordination bonds, then accompanied by a release of Cu(II) that would induce the electrostatic aggregation of GNPs for photo-thermal ablation; furthermore, the significantly enhanced chemotherapy efficiency could be achieved by PDT produced hypoxia to reduce AQ4N into AQ4. Taken together, here described nanoplatform with tumor cell specific responsive properties and programmable PDT/PTT/chemotherapy functions, might be an interesting synergistic strategy for HCC treatment.

© 2017 Optical Society of America