Nitric oxide/PDT combination therapy by the fluorescent self-reporting Co-delivery platforms

Abstract

Nitric oxide (NO) combined with photodynamic therapy (PDT) is a promising tumor treatment method. Herein, the cationic lipid DPNO(Zn) was developed as co-delivery carrier of NO and photosensitizer Chlorin e6 (Ce6). The target CNO lipid nanoparticles (LNPs) were obtained by solvent exchange method as a NO/PDT combination therapy platform, and biocompatible polymer γPGA could be easily coated to form PCNO for in vivo applications. Fluorescence spectra and confocal imaging experiments showed that the Ce6-loaded LNPs could release NO rapidly under low power UV irradiation with fluorescence self-reporting ability. On the other hand, under the irradiation of 660 nm laser, the LNPs could effectively produce singlet oxygen (1O2). In vitro and in vivo antitumor assays showed that the combination treatment of NO/PDT was more effective in tumor growth inhibition compared with individual NO or PDT treatment. Mechanism studies of NO/PDT combined therapy revealed that 1O2 could increase the level of p53 protein, thus activating the caspase 3 apoptosis pathway. And the rapid release of NO could amplify the effect of this pathway by reducing the level of HIF-1α. The NO and 1O2 released under laser irradiation could not only directly damage DNA and mitochondria, resulting in tumor cell dysfunction, but also induce the upregulation of iNOS to further enhance the gas therapy efficiency. This study proved that the light-triggered NO/1O2 generation system can be used as an effective NO/PDT synergistic therapy platform for cancer treatment.