Abstract

Novel nanoscale bioconjugates combining unique plasmonic photothermal properties of gold nanoparticles (AuNPs) with targeted delivery using cell-specific DNA aptamers have a tremendous potential for medical diagnostics and therapy of many cell-based diseases. In this study, we demonstrate the high anti-cancer activity of aptamer-conjugated, 37-nm spherical gold nanoparticles toward Ehrlich carcinoma in tumor-bearing mice after photothermal treatment. The synthetic anti-tumor aptamers bring the nanoparticles precisely to the desired cells and selectively eliminate cancer cells after the subsequent laser treatment. To prove tumor eradication, we used positron emission tomography (PET) utilizing radioactive glucose and computer tomography, followed by histological analysis of cancer tissue. Three injections of aptamer-conjugated AuNPs and 5 min of laser irradiations are enough to make the tumor undetectable by PET. Histological analysis proves PET results and shows lower damage of healthy tissue in addition to a higher treatment efficiency and selectivity of the gold nanoparticles functionalized with aptamers in comparison to control experiments using free unconjugated nanoparticles.

Highlights

  • Gold nanoparticles (AuNPs) are of a great interest for cancer therapy, especially for thermal destruction of tumor cells, due to their photothermal heating ability under laser irradiation and their ability to be surface functionalized

  • The authors used a DNA aptamer previously selected against the A549 human cancer cell line by Cell-SELEX to functionalize Au@Ag/Au NPs via the thiol-gold bond to achieve specific NIR Photothermal therapy (PTT)

  • We demonstrate the PTT activity of aptamer-conjugated 37-nm spherical gold nanoparticles (As42-AuNPs) toward Ehrlich carcinoma cells in tumor-bearing mice (Figure 1)

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Summary

Introduction

Gold nanoparticles (AuNPs) are of a great interest for cancer therapy, especially for thermal destruction of tumor cells, due to their photothermal heating ability under laser irradiation and their ability to be surface functionalized. Photothermal therapy (PTT) is currently considered to be a relatively noninvasive and benign alternative for cancer treatment.[2] To deliver nanoparticles to tumor sites, monoclonal antibodies (mAbs) are successfully used for the photodestruction of cancer cells and subsequent cell death.[3] An alternative to antibodies as a nanoparticle delivery vehicle is aptamers. Shi et al reported a novel activatable theranostic nanoprobe based on aptamers for in vivo cancer imaging and guided PTT.[4] The authors used a DNA aptamer previously selected against the A549 human cancer cell line by Cell-SELEX to functionalize Au@Ag/Au NPs via the thiol-gold bond to achieve specific NIR PTT. Due to the broad absorption spectra of Au@Ag/Au NPs and the expansion of aptamer discovery for varying cancer targets, aptamer-modified gold nanoparticles can be explored for the treatment of other cancer types

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