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Design of Dense Brush Conformation Bearing Gold Nanoparticles as Theranostic Agent for Cancer

  • Nihan Verimli
  • Ayşegül Demiral
  • Hülya Yılmaz
  • Mustafa Çulha
  • S. Sibel ErdemEmail author
Article
  • 20 Downloads

Abstract

Dense brush conformation–bearing theranostic agents are emerging as drug delivery systems due to their higher ability to escape from reticuloendothelial system uptake which prolongs their in vivo circulation time. With the aim of developing dual therapy agent, 13-nm gold nanoparticles’ (AuNPs) surfaces were coated with different amounts of polyethylene glycol (PEG) (SH-PEG-NH2) to obtain dense brush conformation–bearing theranostic agents. Among the 14 different theranostic agent candidates prepared, the one hosting 1819 PEG per particle was selected as the most promising theranostic agent candidate based on structural conformation, stability, size, zeta potential, hemocompatibility, cell inhibition, and cell death pathway towards MCF-7 cell line. To test drug delivery efficiency of the developed PEGylated AuNP and to improve efficacy of the treatment, apoptotic peptide (AP) was covalently conjugated to NH2 terminus of the PEG in various ratios to yield AuNP-AP conjugate. Among the prepared conjugates, the one having 1 nmol of peptide per milliliter of AuNP yielded the most promising results based on the same criteria as employed for PEGylated AuNPs. Besides, incorporation of AP to AuNP returned in superior efficacy of AP since it was possible to achieve 50% cell death with 1000 times less amount of AP alone.

Keywords

Apoptosis Apoptotic peptide Breast cancer Drug delivery Gold nanoparticles Hemocompatibility Polyethylene glycol Theranostic agent 

Abbreviations

AP

Apoptotic peptide

BSA

Bovine serum albumin

ATCC

American Type Culture Collection

AuNP

Gold nanoparticle

CT

Computed tomography

D

Distance between two PEG attachments

DLS

Dynamic light scattering

DMEM

Dulbecco’s modified Eagle’s medium

DMSO

Dimethyl sulfoxide

DTNB

5,5′-Dithiobis-(2-nitrobenzoic acid)

EDC

1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide

EPR

Enhanced permeability and retention

FACS

Fluorescence-activated cell sorting

FBS

Fetal bovine serum

FDA

Food and drug administration

IC50

Half maximal inhibitory concentration

LDH

Lactate dehyrdogenase

MTT

(3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

MTS

3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium

NHS

N-hydroxysuccinimide

PBS

Phosphate-buffered saline

PdI

Polydispersity index

PEG

Polyethylene glycol

PEI

Polyethyleneimine

RES

Reticuloendothelial system

Rf

Flory radius

S

Number of PEG per nanoparticles’ surface area

SERS

Surface-enhanced Raman scattering

SH

Sulfhydryl

SPR

Surface plasmon resonance

TEM

Transmission electron microscopy

UV

Ultraviolet

WST

Water-soluble tetrazolium salt

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Issues

Istanbul Medipol University Non-Invasive Clinical Research Ethical Committee with issue number 10840098-604.01.01.-E.16355.

Supplementary material

12010_2019_3151_MOESM1_ESM.docx (92 kb)
ESM 1 (DOCX 91 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.International School of Medicine, Medical BiochemistryIstanbul Medipol UniversityIstanbulTurkey
  2. 2.Regenerative and Restorative Medical Research Center (REMER)IstanbulTurkey
  3. 3.School of Engineering and Natural Sciences, Biomedical EngineeringIstanbul Medipol UniversityIstanbulTurkey
  4. 4.Faculty of Engineering, Department of Genetics and BioengineeringYeditepe UniversityIstanbulTurkey

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