G4-Hemin loaded 2D nanosheets for combined and targeted chemo-photodynamic cancer therapy

Abstract

Synergetic combination therapy, wherein the therapeutic action of one of the components assists the therapeutic performance of the second agent, is emerging as one of the most promising approaches for cancer treatment. Among the various therapeutic approaches for cancer, photodynamic therapy (PDT) has received particular attention due to its non-invasive nature and spatiotemporal controllability. However, therapeutic performance of PDT is severally affected by tumour hypoxia. Herein, we report a supramolecular strategy for the fabrication of a PDT active 2D nanosheet loaded with a peroxidase enzyme-mimicking DNAzyme for the synergetic combination of PDT and chemodynamic therapy (CDT) for targeted cancer therapy. The nanoformulation consists of a cationic photosensitizer-based nanosheet loaded G4-DNA-hemin complex on the surface of the nanosheet via electrostatic interaction. Irradiation of the nanoformulation using 635 nm laser resulted in the generation of reactive oxygen species (ROS) via PDT pathways and toxic radical species via CDT pathway. Importantly, in-situ generation of O2 during the CDT action boost the O2 level in the tumour microenvironment, which resulted in the enhancement of PDT activity and the overall therapeutic performance of the system. Excellent therapeutic efficacy was demonstrated both in vitro and in vivo using MDA-MB-231 cancer cells line as a representative cell line and the enhanced therapeutic performance of the nanoformulation was attributed to the synergetic combination of CDT and PDT. This work represents a unique combination of CDT and PDT for targeted cancer therapy, wherein, CDT action of the nanoagent enhances the PDT efficacy and we strongly believe that this approach would encourage other researchers to design similar combination therapy for the advancements in the treatment of cancer.