Abstract

Safe administration of highly cytotoxic chemotherapeutic drugs is a challenging problem in cancer treatment due to the adverse side effects and collateral damage to non-tumorigenic cells. To mitigate these problems, promising new approaches, based on the paradigm of controlled targeted drug delivery (TDD), and utilizing drug nanocarriers with biorecognition ability to selectively target neoplastic cells, are being considered in cancer therapy. Herein, we report on the design and testing of a nanoparticle-grid based biosensing platform to aid in the development of new targeted drug nanocarriers. The proposed sensor grid consists of superparamagnetic gold-coated core–shell Fe2Ni@Au nanoparticles, further functionalized with folic acid targeting ligand, model thiolated chemotherapeutic drug doxorubicin (DOX), and a biocompatibility agent, 3,6-dioxa-octanethiol (DOOT). The employed dual transduction method based on electrochemical and enhanced Raman scattering detection has enabled efficient monitoring of the drug loading onto the nanocarriers, attaching to the sensor surface, as well as the drug release under simulated intracellular conditions. The grid’s nanoparticles serve here as the model nanocarriers for new TDD systems under design and optimization. The superparamagnetic properties of the Fe2Ni@Au NPs aid in nanoparticles’ handling and constructing a dense sensor grid with high plasmonic enhancement of the Raman signals due to the minimal interparticle distance.

Highlights

  • With the new advances in nanobiotechnology, the targeted drug delivery (TDD) of cytotoxic chemotherapeutics is becoming one of the most promising approaches in cancer treatment [1,2,3]

  • The drug loading onto the nanocarriers was closely monitored with surface-enhanced RAMAN scattering (SERS) and electrochemical relaxation methods: cyclic voltammetry (CV) and differential-pulse voltammetry (DPV)

  • The surface-enhanced Raman light scattering (SERS) sensor in this work refers to a magneto-plasmonic nanogrid Raman sensor (MPR sensor); The electrochemical sensor, formed on a polycrystalline Au-disk electrode (AuDE), was coated with two structural layers of reduced graphene oxide nanosheets (rGO) and magnetic nanoparticles (MNPs) grid, and had the composition: AuDE@CYS/rGO@PATP/MNP@mercapto-propionic acid (MPA)

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Summary

Introduction

With the new advances in nanobiotechnology, the targeted drug delivery (TDD) of cytotoxic chemotherapeutics is becoming one of the most promising approaches in cancer treatment [1,2,3]. The TDD systems are based on drug nanocarriers, equipped with biorecognition capability, directed toward cancer cells [4,5]. We have investigated new platforms for designing and testing model drug nanocarriers for future applications in new TDD systems. The proposed novel biosensing platform is based on a monolayer of model nanocarriers immobilized on a Au(111) substrate or a gold disk electrode (AuDE). The nanocarriers consist of superparamagnetic gold-coated Fe2 Ni@Au core–shell nanoparticles, functionalized with a chemotherapeutic drug doxorubicin (DOX) and other functional molecules.

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