Cell membranes targeted unimolecular prodrug for programmatic photodynamic-chemo therapy.

ABSTRACT: Photodynamic therapy (PDT) has emerged as one of the most up-and-coming non-invasive therapeutic modalities for cancer therapy in rencent years. However, its therapeutic effect was still hampered by the short life span, limited diffusion distance and ineluctable depletion of singlet oxygen (¹O₂), as well as the hypoxic microenvironment in the tumor tissue. Such problems have limited the application of PDT and appropriate solutions are highly demand. Methods: Herein, a programmatic treatment strategy is proposed for the development of a smart molecular prodrug (D-bpy), which comprise a two-photon photosensitizer and a hypoxia-activated chemotherapeutic prodrug. A rhodamine dye was designed to connect them and track the drug release by the fluorescent signal generated through azo bond cleavage. Results: The prodrug (D-bpy) can stay on the cell membrane and enrich at the tumor site. Upon light irradiation, the therapeutic effect was enhanced by a stepwise treatment: (i) direct generation of ¹O₂ on the cell membrane induced membrane destruction and promoted the D-bpy uptake; (ii) deep tumor hypoxia caused by two-photon PDT process further triggered the activation of the chemotherapy prodrug. Both in vitro and in vivo experiments, D-bpy have exhabited excellent tumor treatment effect. Conclusion: The innovative programmatic treatment strategy provides new strategy for the design of follow-up anticancer drugs.

SUBMITTER: Yuan J 

PROVIDER: S-EPMC7847693 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature