Gold nanostar-polymer hybrids for siRNA delivery: Polymer design towards colloidal stability and in vitro studies on breast cancer cells

Carla Sardo, Gennara Cavallaro, Cinzia Scialabba, Emanuela Fabiola Craparo, Gaetano Giammona, Giacomo Dacarro, Elisa Cabrini, Agnese D'Agostino, Barbara Bassi, Piersandro Pallavicini, Angelo Taglietti

Risultato della ricerca: Article

8 Citazioni (Scopus)

Abstract

To overcome the low bioavailability of siRNA (small interfering RNA) and to improve their transfection efficiency, the use of non-viral delivery carriers is today a feasible approach to transform the discovery of these incredibly potent and versatile drugs into clinical practice. Polymer-modified gold nanoconstructs (AuNCs) are currently viewed as efficient and safe intracellular delivery carriers for siRNA, as they have the possibility to conjugate the ability to stably entrap and deliver siRNAs inside cells with the advantages of gold nanoparticles, which can act as theranostic agents and radiotherapy enhancers through laser-induced hyperthermia. In this study, AuNCs were prepared by coating Gold Nano Stars (GNS) with suitable functionalised polymers, to give new insight on the choice of the coating in order to obtain colloidal stability, satisfying in vitro transfection behaviour and reliability in terms of homogeneous results upon GNS type changing. For this goal, GNS synthesized with three different sizes and shapes were coated with two different polymers: i) α-mercapto-Ï-amino polyethylene glycol 3000 Da (SH-PEG3000-NH2), a hydrophilic linear polymer; ii) PHEA-PEG2000-EDA-LA (PPE-LA), an amphiphilic hydroxyethylaspartamide copolymer containing a PEG moiety. Both polymers contain [sbnd]SH or [sbnd]SS[sbnd] groups for anchoring on gold surface and NH2groups, which can be protonated in order to obtain a positive surface for successive siRNA layering. The effect of the features of the coating polymers on siRNA layering, and the extent of intracellular uptake and luciferase gene silencing effect were evaluated for each of the obtained coated GNS. The results highlight that amphiphilic biocompatible polymers with multi-grafting function are more suitable for ensuring the colloidal stability and the effectiveness of these colloidal systems, compared to the coating with linear PEG.
Lingua originaleEnglish
pagine (da-a)113-124
Numero di pagine12
RivistaInternational Journal of Pharmaceutics
Volume519
Stato di pubblicazionePublished - 2017

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Gold
Small Interfering RNA
Polymers
Breast Neoplasms
Transfection
Induced Hyperthermia
Gene Silencing
In Vitro Techniques
Luciferases
Nanoparticles
Biological Availability
Lasers
Radiotherapy
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

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Gold nanostar-polymer hybrids for siRNA delivery: Polymer design towards colloidal stability and in vitro studies on breast cancer cells. / Sardo, Carla; Cavallaro, Gennara; Scialabba, Cinzia; Craparo, Emanuela Fabiola; Giammona, Gaetano; Dacarro, Giacomo; Cabrini, Elisa; D'Agostino, Agnese; Bassi, Barbara; Pallavicini, Piersandro; Taglietti, Angelo.

In: International Journal of Pharmaceutics, Vol. 519, 2017, pag. 113-124.

Risultato della ricerca: Article

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abstract = "To overcome the low bioavailability of siRNA (small interfering RNA) and to improve their transfection efficiency, the use of non-viral delivery carriers is today a feasible approach to transform the discovery of these incredibly potent and versatile drugs into clinical practice. Polymer-modified gold nanoconstructs (AuNCs) are currently viewed as efficient and safe intracellular delivery carriers for siRNA, as they have the possibility to conjugate the ability to stably entrap and deliver siRNAs inside cells with the advantages of gold nanoparticles, which can act as theranostic agents and radiotherapy enhancers through laser-induced hyperthermia. In this study, AuNCs were prepared by coating Gold Nano Stars (GNS) with suitable functionalised polymers, to give new insight on the choice of the coating in order to obtain colloidal stability, satisfying in vitro transfection behaviour and reliability in terms of homogeneous results upon GNS type changing. For this goal, GNS synthesized with three different sizes and shapes were coated with two different polymers: i) {\^I}±-mercapto-{\"I}-amino polyethylene glycol 3000 Da (SH-PEG3000-NH2), a hydrophilic linear polymer; ii) PHEA-PEG2000-EDA-LA (PPE-LA), an amphiphilic hydroxyethylaspartamide copolymer containing a PEG moiety. Both polymers contain [sbnd]SH or [sbnd]SS[sbnd] groups for anchoring on gold surface and NH2groups, which can be protonated in order to obtain a positive surface for successive siRNA layering. The effect of the features of the coating polymers on siRNA layering, and the extent of intracellular uptake and luciferase gene silencing effect were evaluated for each of the obtained coated GNS. The results highlight that amphiphilic biocompatible polymers with multi-grafting function are more suitable for ensuring the colloidal stability and the effectiveness of these colloidal systems, compared to the coating with linear PEG.",
keywords = "Gold nanostars; Lipoic acid; MCF-7; PEG; PHEA; siRNA delivery; Biological Availability; Breast Neoplasms; Cell Line, Small Interfering; Reproducibility of Results; Transfection; 3003, Tumor; Drug Carriers; Drug Delivery Systems; Drug Stability; Gene Silencing; Gold; Gold Colloid; Humans; Hydrophobic and Hydrophilic Interactions; MCF-7 Cells; Metal Nanoparticles; Particle Size; Polyethylene Glycols; Polymers; RNA",
author = "Carla Sardo and Gennara Cavallaro and Cinzia Scialabba and Craparo, {Emanuela Fabiola} and Gaetano Giammona and Giacomo Dacarro and Elisa Cabrini and Agnese D'Agostino and Barbara Bassi and Piersandro Pallavicini and Angelo Taglietti",
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T1 - Gold nanostar-polymer hybrids for siRNA delivery: Polymer design towards colloidal stability and in vitro studies on breast cancer cells

AU - Sardo, Carla

AU - Cavallaro, Gennara

AU - Scialabba, Cinzia

AU - Craparo, Emanuela Fabiola

AU - Giammona, Gaetano

AU - Dacarro, Giacomo

AU - Cabrini, Elisa

AU - D'Agostino, Agnese

AU - Bassi, Barbara

AU - Pallavicini, Piersandro

AU - Taglietti, Angelo

PY - 2017

Y1 - 2017

N2 - To overcome the low bioavailability of siRNA (small interfering RNA) and to improve their transfection efficiency, the use of non-viral delivery carriers is today a feasible approach to transform the discovery of these incredibly potent and versatile drugs into clinical practice. Polymer-modified gold nanoconstructs (AuNCs) are currently viewed as efficient and safe intracellular delivery carriers for siRNA, as they have the possibility to conjugate the ability to stably entrap and deliver siRNAs inside cells with the advantages of gold nanoparticles, which can act as theranostic agents and radiotherapy enhancers through laser-induced hyperthermia. In this study, AuNCs were prepared by coating Gold Nano Stars (GNS) with suitable functionalised polymers, to give new insight on the choice of the coating in order to obtain colloidal stability, satisfying in vitro transfection behaviour and reliability in terms of homogeneous results upon GNS type changing. For this goal, GNS synthesized with three different sizes and shapes were coated with two different polymers: i) α-mercapto-Ï-amino polyethylene glycol 3000 Da (SH-PEG3000-NH2), a hydrophilic linear polymer; ii) PHEA-PEG2000-EDA-LA (PPE-LA), an amphiphilic hydroxyethylaspartamide copolymer containing a PEG moiety. Both polymers contain [sbnd]SH or [sbnd]SS[sbnd] groups for anchoring on gold surface and NH2groups, which can be protonated in order to obtain a positive surface for successive siRNA layering. The effect of the features of the coating polymers on siRNA layering, and the extent of intracellular uptake and luciferase gene silencing effect were evaluated for each of the obtained coated GNS. The results highlight that amphiphilic biocompatible polymers with multi-grafting function are more suitable for ensuring the colloidal stability and the effectiveness of these colloidal systems, compared to the coating with linear PEG.

AB - To overcome the low bioavailability of siRNA (small interfering RNA) and to improve their transfection efficiency, the use of non-viral delivery carriers is today a feasible approach to transform the discovery of these incredibly potent and versatile drugs into clinical practice. Polymer-modified gold nanoconstructs (AuNCs) are currently viewed as efficient and safe intracellular delivery carriers for siRNA, as they have the possibility to conjugate the ability to stably entrap and deliver siRNAs inside cells with the advantages of gold nanoparticles, which can act as theranostic agents and radiotherapy enhancers through laser-induced hyperthermia. In this study, AuNCs were prepared by coating Gold Nano Stars (GNS) with suitable functionalised polymers, to give new insight on the choice of the coating in order to obtain colloidal stability, satisfying in vitro transfection behaviour and reliability in terms of homogeneous results upon GNS type changing. For this goal, GNS synthesized with three different sizes and shapes were coated with two different polymers: i) α-mercapto-Ï-amino polyethylene glycol 3000 Da (SH-PEG3000-NH2), a hydrophilic linear polymer; ii) PHEA-PEG2000-EDA-LA (PPE-LA), an amphiphilic hydroxyethylaspartamide copolymer containing a PEG moiety. Both polymers contain [sbnd]SH or [sbnd]SS[sbnd] groups for anchoring on gold surface and NH2groups, which can be protonated in order to obtain a positive surface for successive siRNA layering. The effect of the features of the coating polymers on siRNA layering, and the extent of intracellular uptake and luciferase gene silencing effect were evaluated for each of the obtained coated GNS. The results highlight that amphiphilic biocompatible polymers with multi-grafting function are more suitable for ensuring the colloidal stability and the effectiveness of these colloidal systems, compared to the coating with linear PEG.

KW - Gold nanostars; Lipoic acid; MCF-7; PEG; PHEA; siRNA delivery; Biological Availability; Breast Neoplasms; Cell Line

KW - Small Interfering; Reproducibility of Results; Transfection; 3003

KW - Tumor; Drug Carriers; Drug Delivery Systems; Drug Stability; Gene Silencing; Gold; Gold Colloid; Humans; Hydrophobic and Hydrophilic Interactions; MCF-7 Cells; Metal Nanoparticles; Particle Size; Polyethylene Glycols; Polymers; RNA

UR - http://hdl.handle.net/10447/248387

UR - http://www.elsevier.com/locate/ijpharm

M3 - Article

VL - 519

SP - 113

EP - 124

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

ER -