Antisense DNA loaded 2D nanosheets for combined photodynamic and antisense cancer therapy

Abstract

Recent years have witnessed the rapid growth of combination therapy as a promising strategy for the cancer treatment. Among the various possibilities, combination of PDT and antisense DNA therapy is considered as the most promising strategy. Herein, a new supramolecular strategy for the creation of a multifunctional therapeutic nanosystem that consists of PDT active 2D nanosheets loaded with antisense DNA for the combination of PDT and antisense therapy for the cancer treatment is reported. The therapeutic efficacy of antisense DNA loaded PDT active nanosheets is studied using HeLa cells as the representative cell line. The nanosystem is found to undergo lysosomal escape due to the positively charged surface of the sheets, which is highly beneficial as the lysosomal degradation of the therapeutically active DNA can be significantly reduced. Efficient singlet oxygen generation inside the cancer cells upon NIR light irradiation of the sheets is shown. In addition, downregulation of the anti-apoptotic protein Bcl-2 by the action of antisense DNA is also demonstrated. Excellent therapeutic efficacy is observed for the antisense DNA loaded nanosheets under NIR light irradiation when compared to the individual therapeutic agents. The enhanced therapeutic efficacy of the nanohybrid system is attributed to the synergetic combination of the PDT action of the nanosheets and the antisense action of the DNA. Our design strategy demonstrates the self-delivery of functional nucleic acids along with PDT active nanomaterials for synergistic and cooperative cancer therapy.