Advanced nanocarriers for an antitumor peptide

Pippa, Νatassa; Pispas, Stergios; Demetzos, Costas; Sivolapenko, Gregory

doi:10.1007/s11051-013-2062-y

Cited by 8 publications

(10 citation statements)

References 72 publications

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“…Conjugation of DOX to AuPEG_1 surface was carried out as from previous published work, 38,40,41 using a carbodiimide-based conjugation of the carboxylic-terminated polymer and forming AuPEG_3. Briefly, 20 μL of EDC/NHS (80/20 mg ratio) aqueous solution was added to 5 mL of AuPEG_1.…”

Section: Doxorubicin Loading Onto Aupeg_1 and Formation Of Aupeg_3mentioning

confidence: 99%

Targeted polyethylene glycol gold nanoparticles for the treatment of pancreatic cancer: from synthesis to proof-of-concept in vitro studies

Spadavecchia¹,

Movia²,

Moore³

et al. 2016

IJN

167

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International audienceThe main objective of this study was to optimize and characterize a drug delivery carrier for doxorubicin, intended to be intravenously administered, capable of improving the therapeutic index of the chemotherapeutic agent itself, and aimed at the treatment of pancreatic cancer. In light of this goal, we report a robust one-step method for the synthesis of dicarboxylic acid-terminated polyethylene glycol (PEG)-gold nanoparticles (AuNPs) and doxorubicin-loaded PEG-AuNPs, and their further antibody targeting (anti-Kv11.1 polyclonal antibody [pAb]). In in vitro proof-of-concept studies, we evaluated the influence of the nanocarrier and of the active targeting functionality on the anti-tumor efficacy of doxorubicin, with respect to its half-maximal effective concentration (EC50) and drug-triggered changes in the cell cycle. Our results demonstrated that the therapeutic efficacy of doxorubicin was positively influenced not only by the active targeting exploited through anti-Kv11.1-pAb but also by the drug coupling with a nanometer-sized delivery system, which indeed resulted in a 30-fold decrease of doxorubicin EC50, cell cycle blockage, and drug localization in the cell nuclei. The cell internalization pathway was strongly influenced by the active targeting of the Kv11.1 subunit of the human Ether-à-go-go related gene 1 (hERG1) channel aberrantly expressed on the membrane of pancreatic cancer cells. Targeted PEG-AuNPs were translocated into the lysosomes and were associated to an increased lysosomal function in PANC-1 cells. Additionally, doxorubicin release into an aqueous environment was almost negligible after 7 days, suggesting that drug release from PEG-AuNPs was triggered by enzymatic activity. Although preliminary, data gathered from this study have considerable potential in the application of safe-by-design nano-enabled drug-delivery systems (ie, nanomedicines) for the treatment of pancreatic cancer, a disease with a poor prognosis and one of the main current burdens of today’s health care bill of industrialized countries

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Section: Doxorubicin Loading Onto Aupeg_1 and Formation Of Aupeg_3mentioning

confidence: 99%

Targeted polyethylene glycol gold nanoparticles for the treatment of pancreatic cancer: from synthesis to proof-of-concept in vitro studies

Spadavecchia¹,

Movia²,

Moore³

et al. 2016

IJN

167

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show abstract

“…As previously mentioned, the synthesis and physicochemical characterization of DOX ON–PEG–AuNPs have been recently published by some of the authors. ,− Some differences among the two samples were immediately evident. First, DOX IN–PEG–AuNPs were characterized by a negative zeta potential in water, whereas DOX ON–PEG–AuNPs solutions demonstrated a positive zeta potential.…”

Section: Resultsmentioning

confidence: 90%

Tunable Design of Gold(III)–Doxorubicin Complex–PEGylated Nanocarrier. The Golden Doxorubicin for Oncological Applications

Moustaoui

Movia

Dupont

et al. 2016

ACS Appl. Mater. Interfaces

186

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To date, the translation of Au (III) complexes into chemotherapeutic agents has been hindered by their low stability under physiological conditions, a crucial parameter in drug development. In this study, we report an innovative four-step synthesis of a stable Au (III)-doxorubicin (DOX) complex, acting as a key constitutive component of doxorubicin-loaded PEG-coated nanoparticles (DOX IN-PEG-AuNPs). For therapeutic purposes, such AuNPs were then functionalized with the anti-Kv11.1 polyclonal antibody (pAb), which specifically recognizes the hERG1 channel that is overexpressed on the membrane of human pancreatic cancer cells. The nature of the interactions between DOX and Au (III) ions was probed by various analytical techniques (Raman spectroscopy, UV-vis, and (1)H NMR), which enabled studying the Au (III)-DOX interactions during AuNPs formation. The theoretical characterization of the vibrational bands and the electronic transitions of the Au (III)-DOX complex calculated through computational studies showed significant qualitative agreement with the experimental observations on AuNPs samples. Stability in physiological conditions and efficient drug loading (up to to 85 w/w %) were achieved, while drug release was strongly dependent on the structure of DOX IN-PEG-AuNPs and on the pH. Furthermore, the interactions among DOX, PEG, and Au (III) ions in DOX IN-PEG-AuNPs differed significantly from those found in polymer-modified AuNPs loaded with DOX by covalent linkage, referred to as DOX ON-PEG-AuNPs. In vitro experiments indeed demonstrated that such differences strongly influenced the therapeutic potential of AuNPs in pancreatic cancer treatment, with a significant increase of the DOX therapeutic index when complexed to Au (III) ions. Collectively, our study demonstrated that Au (III)-DOX complexes as building blocks of PEGylated AuNPs constitutes a promising approach to transform promising Au (III) complexes into real chemotherapeutic drugs for the treatment of pancreatic cancer.

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“…As an example of biocompatible functionalization, polyethylene glycol (PEG) and poly N-vinyl-2-pyrrolidone (PVP) were exploited to modify nanovectors for gene drug/delivery [17][18][19] , tumor targeting 20,21 A c c e p t e d M a n u s c r i p t and x-ray imaging 22 . For in vivo applications using PEG-gold nanoparticles, all the preparations were based on conventional methods (i.e.sodium citrate or sodium borohydrate reduction) and post-addition of thiolated PEG leading to gold particles usually larger than 20 nm 23 .…”

Section: Introductionmentioning

confidence: 99%

Polyethylene glycol gold-nanoparticles: Facile nanostructuration of doxorubicin and its complex with DNA molecules for SERS detection

Spadavecchia

Perumal

Casale

et al. 2016

Chemical Physics Letters

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We report the synthesis of dicarboxylic acid-terminated polyethylene-glycol (PEG)-gold nanoparticles by a simple one-step method, and their further use to form nanostructured surfaces for biomolecule immobilization. The synthesized nano-scale particles were conjugated with probe/target oligonucleotides in order to evaluate intercalation phenomenon in the presence of doxorubicin drug via Surface Enhanced Raman Spectroscopy (SERS) analysis.

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Advanced nanocarriers for an antitumor peptide

Cited by 8 publications

References 72 publications

Targeted polyethylene glycol gold nanoparticles for the treatment of pancreatic cancer: from synthesis to proof-of-concept in vitro studies

Targeted polyethylene glycol gold nanoparticles for the treatment of pancreatic cancer: from synthesis to proof-of-concept in vitro studies

Tunable Design of Gold(III)–Doxorubicin Complex–PEGylated Nanocarrier. The Golden Doxorubicin for Oncological Applications

Polyethylene glycol gold-nanoparticles: Facile nanostructuration of doxorubicin and its complex with DNA molecules for SERS detection

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