Electrochemical Methods for Probing DNA Damage Mechanisms and Designing Cisplatin-Based Combination Chemotherapy

Abstract

An electrochemical approach was devised for detecting DNA damage and differentiating two DNA damage mechanisms, which is important to the design of new chemotherapeutics. This approach combined two platforms, based on the detection of base damage and DNA strand cleavage. In this work, our approach was demonstrated for the detection of cisplatin-induced DNA damage and the enhancement effects of two electron donors, N,N,N,N-tetramethyl-p-phenylenediamine (TMPD) and reduced graphene oxide (rGO). Our results demonstrated that TMPD enhanced DNA strand cleavage, supporting the proposed dissociative electron transfer mechanism. While rGO, which is an efficient electron donor, failed to show any enhancement (suggesting the lack of free-radical generation), overall, this electrochemical approach could be implemented for discoveringnext-generation DNA damage-based chemotherapy drugs.

Ultralight 3D Graphene Oxide Aerogel Decorated with Pd–Fe Nanoparticles for the Simultaneous Detection of Eight Biomolecules

“…We hypothesized that this peak was due to the formation of the G-cisplatin complex or simply the excess cisplatin being oxidized at the electrode surface. This hypothesis was based on previously published articles that reported the pronounced anodic peak of cisplatin between 0.64 and 1 V vs Ag/AgCl. , …”

“…This hypothesis was based on previously published articles that reported the pronounced anodic peak of cisplatin between 0.64 and 1 V vs Ag/AgCl. 69,70…”

2D Nanomaterials and Their Drug Conjugates for Phototherapy and Magnetic Hyperthermia Therapy of Cancer and Infections

“…Other 2DnMat tested for photothermal treatment of cancer or infections have also shown to be biocompatible. [ 19,62a,b,d‐f,h,66,109 ] Pd nanosheets were tested by different authors in a wide range of concentrations (2.5‐1000 µg mL −1 ) using different cell lines. [ 19,62d,h ] Tang et al.…”

“…2DnMat have also been conjugated with polymers, proteins, metals, and targeting moieties via covalent or non‐covalent interactions. [ 5,8b,15,17,19,33a‐h,j‐p,43–45,47,50a,c,e,g‐r,54,55e,56b,c,59a,c,61,62d‐h,64–66 , 76e,f,79,90,94f,i,108h,109,138,141 ] Polymers and protein conjugations using PEG and BSA were widely explored and revealed to improve materials stability in physiological media, in vitro and in vivo biocompatibility, and to facilitate the adsorption of other molecules. [ 33a,b,e,h,i,k,o,p,44,45,50a,c,g,i‐k,m,q,r,56d,59b,62b,e,g,h,66,90,107c ] 2DnMat conjugation with IONP, Fe 3 O 4 and other metals (e.g., Co) is often used to provide magnetic properties to the materials, allowing their use as MHT agents.…”