Abstract

Multi-modal nanoprobes have attracted much attention because of their superior chemical and physical properties that have great potential for early diagnosis and treatment of cancer. We report herein a novel stepwise fabrication of a gold nanoparticle-Raman reporter-photosensitiser conjugate called a Gold Nanosensitiser (NS). The efficacy of gold NS as multimodal nanoprobes for surface enhanced Raman spectroscopy (SERS) imaging and photodynamic (PDT) and photothermal treatment (PTT) of cancer were examined. NS were constructed using a multilayer technique in which a Raman reporter, DTTCI (3,3’-Diethylthiatricarbocyanine iodide) and a photosensitiser, hypericin, were coated onto gold nanostars. By adjusting the layer spacing, these coatings endowed NS with both enhanced SERS and fluorescence bioimaging capabilities. Excitation of the NS in solution at an appropriate wavelength permitted examination of the photodynamic therapy (PDT) capability in terms of singlet oxygen generation. As the nanostar is multibranched and comprises multiple ‘hot spots’ capable of enhanced electromagnetic radiation, along with SERS it also exhibits photothermal therapy (PTT) capability when excited at its resonant wavelength of 675 nm. The NS was also characterised to examine the retention of physio-chemical and optical properties of its components after fabrication. The development of such a multimodal nanoplatform in the current work will offer a useful tool for noninvasive, high-accuracy, single-node diagnosis and therapy of cancer.

Highlights

  • In the recent past, there have been accelerated developments in biomedical modalities for the early diagnosis and therapy of cancer

  • A pH of 7.4 was selected for further synthesis for two reasons; it is close to the physiological pH and, at this pH, nanostars with narrower absorption bands and high monodispersity were produced

  • Multibranched gold nanostars were synthesised based on a green chemistry approach using HEPES as a reducing and shape directing agent

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Summary

Introduction

There have been accelerated developments in biomedical modalities for the early diagnosis and therapy of cancer. Most of the PSs are hydrophobic in nature which makes systemic administration problematic and, in turn, affects its delivery to and uptake by tumour cells [2,3] They tend to aggregate, which reduces the quantum efficiency of ROS generation. This has led to the development of third-generation PS that are equipped with nanocarrier systems to enhance their targeted delivery for efficient PDT and photodynamic diagnosis (PDD). These nanocarriers, which load PS by physisorption or covalent binding, offer benefits of hydrophilicity and appropriate size for passive targeting of tumour by the enhanced permeability and retention (EPR) effect. Strong absorption and scattering of gold nanoparticles provides opportunities for contrast enhanced optical imaging

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