Development of Theranostics for Viral Disease and Cancer based on Carbon Nanomaterials

Abstract

Many recalcitrant diseases have its origin in the undesirable biological processes at molecular levels such as gene mutation, protein dysfunction, and viral infection. The field of nanomedicine approaches to apply the chemical/physical characteristics of nanomaterials for the diagnosis and treatment of viral diseases and cancer at the molecular level. Among the various type of nanomaterials, herein, we focus on the carbon nanomaterials possessing unique physicochemical properties, giving rise to the great potential for the diagnosis and therapy of viral disease or cancer. Carbon nanomaterials exhibit several characteristics including high specific surface areas and sp2/sp3 hybridized carbon atoms. Therefore, they have simple relationships with biomolecules through novel strategies of surface modification. This approach enables chemical or physical interaction with biomolecules facilitating improved biocompatibility and controlling their properties in biological systems. In this study, we reported four therapeutic systems including biological imaging, drug/gene delivery, and photodynamic therapy that are classified into two categories according to carbon allotrope

graphene oxide (GO) and carbon nanodot (CD).

First, we developed multifunctional DNAzyme (Dz) delivery system based on nano-sized graphene oxide (nGO) for simultaneous detection and knockdown of the target gene. The Dz/nGO complex system allowed convenient monitoring of hepatitis C virus (HCV) mRNA in living cells and silencing of the HCV gene expression by Dz-mediated catalytic cleavage concurrently.

Second, we design a dual action of the antibiotic drug and synthetic RNA based on the functionalized GO mediated co-delivery system and demonstrate its synergistic effect in vitro and in liver cancer cell xenograft mouse model representing HCV infection. We find that our strategy successfully improves the therapeutic efficacy by suppressing the tumor growth through enhancing intracellular accumulation of antibiotic drug with one-tenth of conventional dosage and inhibiting replication of viral RNA at the molecular level through small interfering RNA (siRNA)-mediated sequence-specific messenger RNA (mRNA) cleavage.

Third, we describe a novel design of highly biocompatible, fluorescent, folic acid (FA) and PEG-functionalized CD as carriers for zinc phthalocyanine (ZnPc) PS to achieve simultaneous biological imaging and targeted photodynamic therapy. CD-PEG-FA/ZnPc exhibits excellent targeted delivery of the PS, leading to simultaneous imaging and significant targeted photodynamic therapy after irradiation in vitro and in vivo.

Finally, we report a strategy for therapeutic RNA interference (RNAi) based on the highly biocompatible and fluorescent CD in which siRNAs are protected from RNase mediated degradation and have a longer half-life in vivo. Our strategy allows simultaneous bioimaging and efficient down-regulation of gene expression, showing high potential for gene therapy in vitro and in vivo.

We believe that these studies can provide a strong foundation for basic research in the field of nanomedicine and the long-term technical progress of nanotechnology into an effective clinical application.