Multifaceted peptide assisted one-pot synthesis of gold nanoparticles for plectin-1 targeted gemcitabine delivery in pancreatic cancer

Krishnendu Pal, Farah Al-Suraih, Roberto Gonzalez-Rodriguez, Shamit Kumar Dutta, Enfeng Wang, H. Shaun Kwak, Thomas Caulfield, Jeffery L. Coffer, Santanu Bhattacharya

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

An astute modification of the plectin-1-targeting peptide KTLLPTP by introducing a C-terminal cysteine preceded by a tyrosine residue imparted a reducing property to the peptide. This novel property is then exploited to fabricate gold nanoparticles (GNP) via an in situ reduction of gold(iii) chloride in a one-pot, green synthesis. The modified peptide KTLLPTPYC also acts as a template to generate highly monodispersed, spherical GNPs with a narrow size distribution and improved stability. Plectin-1 is known to be aberrantly expressed in the surface of pancreatic ductal adenocarcinoma (PDAC) cells while showing cytoplasmic expression in normal cells. The synthesized GNPs are thus in situ surface modified with the peptides via the cysteine residue leaving the N-terminal KTLLPTP sequence free for targeting plectin-1. The visual molecular dynamics based simulations support the experimental observations like particle size, gemcitabine conjugation and architecture of the peptide-grafted nanoassembly. Additionally, GNPs conjugated to gemcitabine demonstrate significantly higher cytotoxicity in vitro in two established PDAC cell lines (AsPC-1 and PANC-1) and an admirable in vivo antitumor efficacy in a PANC-1 orthotopic xenograft model through selective uptake in PDAC tumor tissues. Altogether, this strategy represents a unique method for the fabrication of a GNP based targeted drug delivery platform using a multifaceted peptide that acts as reducing agent, template for GNP synthesis and targeting agent to display remarkable selectivity towards PDAC.

Original languageEnglish (US)
Pages (from-to)15622-15634
Number of pages13
JournalNanoscale
Volume9
Issue number40
DOIs
StatePublished - Oct 28 2017

Fingerprint

gemcitabine
Plectin
Gold
Peptides
Nanoparticles
Cysteine
Reducing Agents
Reducing agents
Cytotoxicity
Heterografts
Tyrosine
Molecular dynamics
Chlorides
Tumors
Particle size
Cells
Tissue
Fabrication

ASJC Scopus subject areas

  • Materials Science(all)

Cite this

Multifaceted peptide assisted one-pot synthesis of gold nanoparticles for plectin-1 targeted gemcitabine delivery in pancreatic cancer. / Pal, Krishnendu; Al-Suraih, Farah; Gonzalez-Rodriguez, Roberto; Dutta, Shamit Kumar; Wang, Enfeng; Kwak, H. Shaun; Caulfield, Thomas; Coffer, Jeffery L.; Bhattacharya, Santanu.

In: Nanoscale, Vol. 9, No. 40, 28.10.2017, p. 15622-15634.

Research output: Contribution to journalArticle

Pal, Krishnendu ; Al-Suraih, Farah ; Gonzalez-Rodriguez, Roberto ; Dutta, Shamit Kumar ; Wang, Enfeng ; Kwak, H. Shaun ; Caulfield, Thomas ; Coffer, Jeffery L. ; Bhattacharya, Santanu. / Multifaceted peptide assisted one-pot synthesis of gold nanoparticles for plectin-1 targeted gemcitabine delivery in pancreatic cancer. In: Nanoscale. 2017 ; Vol. 9, No. 40. pp. 15622-15634.
@article{32ad9fe1c94949da8f0d6f176efb768b,
title = "Multifaceted peptide assisted one-pot synthesis of gold nanoparticles for plectin-1 targeted gemcitabine delivery in pancreatic cancer",
abstract = "An astute modification of the plectin-1-targeting peptide KTLLPTP by introducing a C-terminal cysteine preceded by a tyrosine residue imparted a reducing property to the peptide. This novel property is then exploited to fabricate gold nanoparticles (GNP) via an in situ reduction of gold(iii) chloride in a one-pot, green synthesis. The modified peptide KTLLPTPYC also acts as a template to generate highly monodispersed, spherical GNPs with a narrow size distribution and improved stability. Plectin-1 is known to be aberrantly expressed in the surface of pancreatic ductal adenocarcinoma (PDAC) cells while showing cytoplasmic expression in normal cells. The synthesized GNPs are thus in situ surface modified with the peptides via the cysteine residue leaving the N-terminal KTLLPTP sequence free for targeting plectin-1. The visual molecular dynamics based simulations support the experimental observations like particle size, gemcitabine conjugation and architecture of the peptide-grafted nanoassembly. Additionally, GNPs conjugated to gemcitabine demonstrate significantly higher cytotoxicity in vitro in two established PDAC cell lines (AsPC-1 and PANC-1) and an admirable in vivo antitumor efficacy in a PANC-1 orthotopic xenograft model through selective uptake in PDAC tumor tissues. Altogether, this strategy represents a unique method for the fabrication of a GNP based targeted drug delivery platform using a multifaceted peptide that acts as reducing agent, template for GNP synthesis and targeting agent to display remarkable selectivity towards PDAC.",
author = "Krishnendu Pal and Farah Al-Suraih and Roberto Gonzalez-Rodriguez and Dutta, {Shamit Kumar} and Enfeng Wang and Kwak, {H. Shaun} and Thomas Caulfield and Coffer, {Jeffery L.} and Santanu Bhattacharya",
year = "2017",
month = "10",
day = "28",
doi = "10.1039/c7nr03172f",
language = "English (US)",
volume = "9",
pages = "15622--15634",
journal = "Nanoscale",
issn = "2040-3364",
publisher = "Royal Society of Chemistry",
number = "40",

}

TY - JOUR

T1 - Multifaceted peptide assisted one-pot synthesis of gold nanoparticles for plectin-1 targeted gemcitabine delivery in pancreatic cancer

AU - Pal, Krishnendu

AU - Al-Suraih, Farah

AU - Gonzalez-Rodriguez, Roberto

AU - Dutta, Shamit Kumar

AU - Wang, Enfeng

AU - Kwak, H. Shaun

AU - Caulfield, Thomas

AU - Coffer, Jeffery L.

AU - Bhattacharya, Santanu

PY - 2017/10/28

Y1 - 2017/10/28

N2 - An astute modification of the plectin-1-targeting peptide KTLLPTP by introducing a C-terminal cysteine preceded by a tyrosine residue imparted a reducing property to the peptide. This novel property is then exploited to fabricate gold nanoparticles (GNP) via an in situ reduction of gold(iii) chloride in a one-pot, green synthesis. The modified peptide KTLLPTPYC also acts as a template to generate highly monodispersed, spherical GNPs with a narrow size distribution and improved stability. Plectin-1 is known to be aberrantly expressed in the surface of pancreatic ductal adenocarcinoma (PDAC) cells while showing cytoplasmic expression in normal cells. The synthesized GNPs are thus in situ surface modified with the peptides via the cysteine residue leaving the N-terminal KTLLPTP sequence free for targeting plectin-1. The visual molecular dynamics based simulations support the experimental observations like particle size, gemcitabine conjugation and architecture of the peptide-grafted nanoassembly. Additionally, GNPs conjugated to gemcitabine demonstrate significantly higher cytotoxicity in vitro in two established PDAC cell lines (AsPC-1 and PANC-1) and an admirable in vivo antitumor efficacy in a PANC-1 orthotopic xenograft model through selective uptake in PDAC tumor tissues. Altogether, this strategy represents a unique method for the fabrication of a GNP based targeted drug delivery platform using a multifaceted peptide that acts as reducing agent, template for GNP synthesis and targeting agent to display remarkable selectivity towards PDAC.

AB - An astute modification of the plectin-1-targeting peptide KTLLPTP by introducing a C-terminal cysteine preceded by a tyrosine residue imparted a reducing property to the peptide. This novel property is then exploited to fabricate gold nanoparticles (GNP) via an in situ reduction of gold(iii) chloride in a one-pot, green synthesis. The modified peptide KTLLPTPYC also acts as a template to generate highly monodispersed, spherical GNPs with a narrow size distribution and improved stability. Plectin-1 is known to be aberrantly expressed in the surface of pancreatic ductal adenocarcinoma (PDAC) cells while showing cytoplasmic expression in normal cells. The synthesized GNPs are thus in situ surface modified with the peptides via the cysteine residue leaving the N-terminal KTLLPTP sequence free for targeting plectin-1. The visual molecular dynamics based simulations support the experimental observations like particle size, gemcitabine conjugation and architecture of the peptide-grafted nanoassembly. Additionally, GNPs conjugated to gemcitabine demonstrate significantly higher cytotoxicity in vitro in two established PDAC cell lines (AsPC-1 and PANC-1) and an admirable in vivo antitumor efficacy in a PANC-1 orthotopic xenograft model through selective uptake in PDAC tumor tissues. Altogether, this strategy represents a unique method for the fabrication of a GNP based targeted drug delivery platform using a multifaceted peptide that acts as reducing agent, template for GNP synthesis and targeting agent to display remarkable selectivity towards PDAC.

UR - http://www.scopus.com/inward/record.url?scp=85031913942&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85031913942&partnerID=8YFLogxK

U2 - 10.1039/c7nr03172f

DO - 10.1039/c7nr03172f

M3 - Article

C2 - 28991294

AN - SCOPUS:85031913942

VL - 9

SP - 15622

EP - 15634

JO - Nanoscale

JF - Nanoscale

SN - 2040-3364

IS - 40

ER -