title: Gold nanostar-polymer hybrids for siRNA delivery: Polymer design towards colloidal stability and in vitro studies on breast cancer cells.
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-ω-amino polyethylene glycol 3000Da (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 SH or SS 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.
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Laboratory of Biocompatible Polymers, Università degli Studi di Palermo, Via Archirafi 32, 90123 Palermo, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Sardo
authors.affiliation: Dipartimento di Chimica, Università di Pavia, viale Taramelli, 12, 27100 Pavia, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bassi
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Laboratory of Biocompatible Polymers, Università degli Studi di Palermo, Via Archirafi 32, 90123 Palermo, Italy.
authors.forename: Emanuela F
authors.initials: EF
authors.lastname: Craparo
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Laboratory of Biocompatible Polymers, Università degli Studi di Palermo, Via Archirafi 32, 90123 Palermo, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Scialabba
authors.affiliation: Dipartimento di Chimica, Università di Pavia, viale Taramelli, 12, 27100 Pavia, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Cabrini
authors.affiliation: Dipartimento di Chimica, Università di Pavia, viale Taramelli, 12, 27100 Pavia, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Dacarro
authors.affiliation: Dipartimento di Chimica, Università di Pavia, viale Taramelli, 12, 27100 Pavia, Italy.
authors.forename: Agnese
authors.initials: A
authors.lastname: D'Agostino
authors.affiliation: Dipartimento di Chimica, Università di Pavia, viale Taramelli, 12, 27100 Pavia, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Taglietti
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Laboratory of Biocompatible Polymers, Università degli Studi di Palermo, Via Archirafi 32, 90123 Palermo, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Giammona
authors.affiliation: Dipartimento di Chimica, Università di Pavia, viale Taramelli, 12, 27100 Pavia, Italy. Electronic address: piersandro.pallavicini@unipv.it.
authors.forename: Piersandro
authors.initials: P
authors.lastname: Pallavicini
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Laboratory of Biocompatible Polymers, Università degli Studi di Palermo, Via Archirafi 32, 90123 Palermo, Italy. Electronic address: gennara.cavallaro@unipa.it.
authors.forename: Gennara
authors.initials: G
authors.lastname: Cavallaro
mesh_terms: D001682:Biological Availability; D001943:Breast Neoplasms / Q000628:therapy*; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D004355:Drug Stability; D020868:Gene Silencing / Q000187:drug effects; D006046:Gold / Q000737:chemistry*; D017979:Gold Colloid / Q000008:administration & dosage / Q000737:chemistry; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D061986:MCF-7 Cells; D053768:Metal Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism; D015203:Reproducibility of Results; D014162:Transfection / Q000379:methods
chemical_list: D004337:Drug Carriers; D017979:Gold Colloid; D011108:Polymers; D034741:RNA, Small Interfering; D011092:Polyethylene Glycols; D006046:Gold
keywords: Gold nanostars; Lipoic acid; MCF-7; PEG; PHEA; siRNA delivery