Pierangelo Gobbo

Improved methodology for the preparation of water-soluble maleimide-functionalized small gold nanoparticles.

Improved methodology to prepare maleimide-functionalized, water-soluble, small (<3 nm) gold nanoparticles using a retro-Diels-Alder strategy that we developed for similar organic-soluble AuNPs is described. Importantly, our results suggest that a recent paper by Zhu, Waengler, Lennox, and Schirrmacher describing a similar strategy gave results inconsistent with the formation of the titled maleimide-modified AuNP (Zhu, J.; Waengler, C.; Lennox, R. B.; Schirrmacher, R. Langmuir2012, 28, 5508) as the major product, but consistent with the major product being an adduct derived from the hydrolysis of maleimide formed under the conditions used for the required deprotection of the maleimide. Our methodology provides an efficient and accessible route to pure maleimide-modified small AuNPs that circumvents the formation of the hydrolysis product. The maleimide-modified small AuNPs are versatile because they are soluble in water and in a wide range of organic solvents and their reactivity can now be properly exploited as a reactive moiety in Michael addition for bioconjugation studies in aqueous solution.

Facile synthesis of gold nanoparticle (AuNP)–carbon nanotube (CNT) hybrids through an interfacial Michael addition reaction

A CNT-AuNP hybrid has been synthesized through the Michael addition reaction between thiol-functionalized single-wall CNT and small water-soluble Maleimide-AuNP. The resilience and stability of this hybrid nanosystem is ensured by a covalent bond linking the nanoparticle to the CNT and by the fact that the functionalization reaction involves the organic shell of the AuNP and not its metallic core.

Versatile strained alkyne modified water-soluble AuNPs for interfacial strain promoted azide–alkyne cycloaddition (I-SPAAC)

Versatile water- and organic solvent-soluble AuNPs that incorporate an interfacial strained alkyne capable of efficient pour and mix strain promoted interfacial cycloadditions with azide partners have been synthesized and carefully characterized for the first time. The use of XPS to quantitate the loading of the strained alkyne on the AuNPs is noteworthy. The reactivity towards the interfacial strain promoted azide-alkyne cycloaddition reaction was demonstrated by using azide-decorated polymersomes as bioorthogonal reaction partners.

Arresting the time-dependent H2O2 mediated synthesis of gold nanoparticles for analytical detection and preparative chemistry

The time-dependent progression from gold nanosponges (AuNS) to discrete small gold nanoparticles (AuNPs) mediated by H2O2 in MES buffer is blocked by the addition of a thiol, glutathione. This represents an important improvement for the plasmonic ELISA, and also leads to a time-dependent approach for the synthesis of AuNS and AuNPs in water with precise control over nanostructure size.

Peptide-decorated gold nanoparticles via strain-promoted azide–alkyne cycloaddition and post assembly deprotection

A new method combining an interfacial strain-promoted azide–alkyne cycloaddition and post assembly deprotection (SPAAC-PAD) has been developed for the well-defined functionalization of small, water-soluble gold nanoparticles with oligopeptides.

Shine & Click Photo-Induced Interfacial Unmasking of Strained Alkynes on Small Water-Soluble Gold Nanoparticles

In this study, we report the design, synthesis, and characterization of small 3 nm water soluble gold nanoparticles (AuNPs) that feature cyclopropenone-masked strained alkyne moieties capable of undergoing interfacial strain-promoted cycloaddition (i-SPAAC) with azides after exposure to UV-A light. A strained alkyne precursor was incorporated onto AuNPs by direct ligand exchange of a thiol-modified cyclopropenone-masked dibenzocyclooctyne (photoDIBO) ligand. These photoDIBO-AuNPs were characterized by 1 H NMR, IR, and UV/Vis spectroscopy, as well as transmission electron microscopy (TEM) and thermogravimetric analysis (TGA), and the extent of modification was quantified. Upon irradiation with UV-A light, photoDIBO-AuNPs underwent efficient and quantitative regeneration of the parent strained alkyne by photochemical decarbonylation to afford DIBO-derivatized AuNPs. DIBO-AuNPs were found to react cleanly and rapidly (k=5.3×10-2  m-1  s-1 ) by an interfacial strain-promoted alkyne-azide cycloadditon (i-SPAAC) with benzyl azide, which served as a simple model system. Furthermore, DIBO-AuNPs were reacted with various azides and a nitrone (interfacial strain-promoted alkyne-nitrone cycloaddition, i-SPANC) to showcase the generality of this approach for the facile modification of AuNP surfaces and their properties. The cyclopropenone-based photo-triggered click chemistry at the interface of water-soluble AuNPs offers exciting opportunities for the atom-by-atom control and assembly of functional materials for applications in materials and biomaterials science as well as in chemical biology.

Water-soluble gold nanoparticles (AuNP) functionalized with a gadolinium(III) chelate via Michael addition for use as a MRI contrast agent

A contrast agent suitable for magnetic resonance imaging based on small, water soluble gold nanoparticles (AuNP) conjugated to over 50 Gd3+ chelators has been prepared by using an interfacial Michael addition in aqueous media. The resultant chelator-AuNP conjugates have been successfully characterised by 1H NMR spectroscopy, IR spectroscopy, ICP-OES, ζ-potential analysis, TEM and MRI. T1-weighted in vivo images of mouse kidney were obtained using the agent at 9.4 T. A preliminary in vivo experiment produced no ill effects and the clearance profile of the agent suggests it is suitable for animal testing at clinically relevant concentrations.

Electrochemistry of robust gold nanoparticle–glassy carbon hybrids generated using a patternable photochemical approach

Photolysis of diazirine modified small (3.9 ± 0.9 nm) gold nanoparticles (AuNP) generates a reactive interfacial carbene that then reacts via an insertion reaction to covalently attach the AuNP onto glassy carbon (GC) electrodes. This yields GC surfaces that are densely and homogeneously functionalized with AuNP. The AuNP hybrid glassy carbon electrode has been characterised by atomic force microscopy (AFM), energy-dispersive X-ray spectroscopy (EDX), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS). The system is found to be robust to physical and electrochemical stresses due to the covalent bond between the AuNP and the surface formed through the carbene insertion reaction. The conductivity of the AuNP functionalized GC electrode is found to be similar to clean GC, and the AuNP serve to switch on electron transfer. The AuNP can be oxidatively desorbed from the electrode at surprisingly low potential (0.99 V). This yields a monolayer of insulator thiol/thiolate ligands that previously anchored the AuNP to the GC, which gives an interesting switch off effect of the electron transfer. We demonstrate that because the method is photoinitiated this methodology allows for spatial control and the AuNP, which can be photopatterned onto GC surfaces easily. The high stability, the good electrical conductivity, the facility of making patterns, and the ability to tune the physical and chemical properties of AuNP through its ligands, make this new functionalization method suitable for the development of sensors and electronic devices.

Fluorogenic Gold Nanoparticle (AuNP) Substrate: A Model for the Controlled Release of Molecules from AuNP Nanocarriers via Interfacial Staudinger–Bertozzi Ligation

The ability to regulate small-molecule release from metallic nanoparticle substrates offers unprecedented opportunities for nanocarrier-based imaging, sensing, and drug-delivery applications. Herein we report a novel and highly specific release methodology off gold nanoparticle (AuNP) surfaces based on the bioorthogonal Staudinger-Bertozzi ligation. A thiol ligand bearing the molecular cargo, a Rhodamine B dye derivative, was synthesized and used to modify small water-soluble 5 nm AuNPs. Upon incorporation into the AuNP monolayer, we observed efficient quenching of the dye emission, resulting in a very low level of fluorescence emission that provided the baseline from which cargo release was monitored. We examined the ability of these AuNPs to react with azide molecules via Staudinger-Bertozzi ligation on the nanoparticle surface by monitoring the fluorescence emission after the introduction of an organic azide. We observed an immediate increase in emission intensity upon azide addition, which corresponded to the release of the dye into the bulk solution. The 31P NMR spectrum of the AuNP product also agrees with the formation of the ligation product. Thus this system represents a novel and highly specific release methodology off AuNP surfaces that can have potential applications in drug delivery, sensing, and materials science.

Bombesin-functionalized water-soluble gold nanoparticles for targeting prostate cancer: Gold Nanoparticles Targeting Prostate Cancer

Cancer targeting can be used for both tumor diagnosis and therapy. Recently, gold nanoparticles (AuNPs) have found utility in this field as they are very small in size, and thus display an enhanced permeability and retention effect, allowing them to be taken up by tumor cells through “passive targeting.” However, this accumulation is non‐specific. Conversely, AuNPs functionalized with targeting entities such as peptides, antibodies, or small molecules can specifically target tumors through interaction with cancer‐specific protein receptors. In this study, targeted AuNPs were developed using an azide‐modified peptide that was able to react with alkyne‐functionalized AuNPs through an interfacial strain‐promoted azide‐alkyne cycloaddition. Small (3 nm) AuNPs were made water‐soluble through PEGylation and functionalized with dibenzocyclooctyne to add the alkyne functionality. For the targeting entity, a pan‐bombesin peptide ([D‐Phe6,β‐Ala11,Phe13,Nle14]bombesin(6–14)) was chosen as it binds to all four receptor subtypes of the gastrin releasing peptide receptor, which is highly expressed in prostate cancer. Prostate cancer (PC‐3) cells were incubated with the targeted AuNPs and studied via transmission electron microscopy. AuNPs conjugated with bombesin showed higher accumulation in PC‐3 cells than either the blocking or control studies. These results suggest that these small, water‐soluble, bombesin‐functionalized AuNPs have potential applications in targeting prostate cancer as diagnostic or therapeutic entities.