Recent advances in cancer photo-theranostics: the synergistic combination of transition metal complexes and gold nanostructures

AbstractIn this mini review, we highlight advances in the last five years in light-activated cancer theranostics by using hybrid systems consisting of transition metal complexes (TMCs) and plasmonic gold nanostructures (AuNPs). TMCs are molecules with attractive properties and high potential in biomedical application. Due to their antiproliferative abilities, platinum-based compounds are currently first-choice drugs for the treatment of several solid tumors. Moreover, ruthenium, iridium and platinum complexes are well-known for their ability to photogenerate singlet oxygen, a highly cytotoxic reactive species with a key role in photodynamic therapy. Their potential is further extended by the unique photophysical properties, which make TMCs particularly suitable for bioimaging. Recently, gold nanoparticles (AuNPs) have been widely investigated as one of the leading nanomaterials in cancer theranostics. AuNPs—being an inert and highly biocompatible material—represent excellent drug delivery systems, overcoming most of the side effects associated with the systemic administration of anticancer drugs. Furthermore, due to the thermoplasmonic properties, AuNPs proved to be efficient nano-sources of heat for photothermal therapy application. Therefore, the hybrid combination TMC/AuNPs could represent a synergistic merger of multiple functionalities for combinatorial cancer therapy strategies. Herein, we report the most recent examples of TMC/AuNPs systems in in-vitro in-vivo cancer tharanostics application whose effects are triggered by light-exposure in the Vis–NIR region, leading to a spatial and temporal control of the TMC/AuNPs activation for light-mediated precision therapeutics

Thickness control of the silica shell: a way to tune the plasmonic properties of isolated and assembled gold nanorods

AbstractBy combining photophysical measurements with transmission electron microscopy, we proved that the thickness of the silica shell around gold nanorods determines the position of the longitudinal plasmonic band when they are isolated in solution or assembled in solid. The silica thickness has been tuned by modulating the reaction time and the ratio between CTAB-coated gold nanorods and TEOS concentration, obtaining gold nanorods covered by a silica shell with a thickness varying from 3.5 to 24 nm. Considering this shell as a spacer between the gold cores, it is possible to modulate the coupling of the localized surface plasmon resonance (LSPR) of neighboring nanorods. Moreover, the comparison between the extinction spectra in solution and in solid, recorded from nanorods covered by silica shell with different thickness, can be used to estimate the inter-nanoparticles distance required for plasmon interaction. We found that LSPR coupling is effective when the distance between the gold cores is no more than 10 nm. When the distance is greater, the nanorods do not interact with each other

Electrofluorochromism in π-conjugated ionic liquid crystals

Materials in which photoluminescence is modulated by redox processes are known as electrofluorochromic. Intrinsically switchable fluorophores, incorporating both redox and fluorescent moieties, could be ideal electrofluorochromic materials if they possess high fluorescence quantum yields in at least one of their redox states. Fluorescent liquid crystals with redox active centres could combine the above requirements with the advantage to work in bulk anisotropic phases. However, electrofluorochromic liquid crystals have not been reported yet because their synthesis is challenging due to aggregation-caused fluorescent quenching. Here we show the first examples of electrofluorochromic π-conjugated ionic liquid crystals based on thienoviologens. These ordered materials, combining ionic and electronic functions, are highly fluorescence in the bulk state (quantum yield>60%). Their direct electrochemical reduction leads to fast and reversible bulk electrofluorochromic response in both columnar and smectic phases allowing for fluorescence intensity modulation and colour tuning

"Smart" molecular engineering of metallomesogens based on Pt(II) terpyridine coordination complexes

A series of ionic tetracoordinated Pt(II) complexes based on terpyridine ligand were synthesized and characterized. Their chemical structures were engineered by using counterions of different coordination strengths and dimensions, namely non-coordinating BF4, weakly coordinating bulky gallate units, and small and strongly coordinating chlorine (Cl). The complexes containing lipophilic gallate units exhibit low temperature liquid crystalline properties. The mesomorphic properties were investigated by polarized optical microscopy (POM), differential scanning calorimetry (DSC) and X-ray diffraction studies (SWAXS). Photophysical properties were determined in solution and condensed states

Emissive Zn(II) metallomesogen based on tridentate terpyridine ligand

A low temperature liquid crystal based on luminescent terpyridine Zn(II) complex is presented. The induction of the mesomorphic properties was achieved using a lipophilic gallate unit as ancillary ligands. The mesomorphic properties were investigated by polarised optical microscopy (POM), differential scanning calorimetry (DSC), thermogravimetric analysis (TA) and X-ray scattering (SWAXS) of bulk materials, while the optical properties of the complex were investigated in solution and in condensed liquid crystalline states

Photoconductive properties and electronic structure in 3,5-disubstituted 2-(2′-pyridyl)pyrroles coordinated to a Pd(II) salicylideneiminate synthon

The synthesis and the electrochemical, photophysical, structural, and photoconductive properties of three new heteroleptic Pd(II) complexes with various 3′,5′- disubstituted-2-(2′-pyridil) pyrroles H(N^N) as coordinated ligands are reported. The coordination of the metal center was completed by a functionalized Schiff base H(O^N) used as an ancillary ligand. The [(N^N)Pd(O^N)] complexes showed highly interesting photoconductive properties which have been correlated to their electronic and molecular structures. Theoretical density functional theory (DFT) and time-dependent DFT calculations were performed, and the results were confronted with the organization in crystalline phase, allowing to point out that the photoconductive properties are mainly a consequence of an efficient intramolecular ligand-to-metal charge transfer, combined to the proximity between the central metal and the donor moieties in the solid-state molecular stacks. The reported results confirm that these new Pd(II) complexes form a novel class of organometallic photoconductors with intrinsic characteristics suitable for molecular semiconductors applications.Supported by Ministero dell’Istruzione, dell’Universitàe della Ricerca by the ELIOTROPO.Peer reviewe

Gold nanoparticles: where shape becomes essence. Synthesis and characterization of an outstanding nanomaterial

Dottorato di Ricerca in Scienze e Tecnologie Fisiche, Chimiche e dei Materiali. Ciclo XXXUniversità della Calabri

Film organici e inorganici funzionalizzati con complessi metallici fotoattivi

Dottorato di ricerca in Metodologie Chimiche inorganiche,XXI Ciclo, a.a. 2007-2008Università della Calabri

Bio-medicinal applications of coordination compounds: a photophysical point of view

Dottorato di Ricerca in Science and Technique Inorganic Chemistry Methods, Bernardino Telesio, Cycle XXV, a.a. 2011-2012Il presente lavoro di ricerca, svolto presso il Laboratorio di Chimica Inorganica e di Coordinazione (LaCIC) dell'Università della Calabria, sotto la supervisione del Dott. Massimo La Deda, e in parte nel Laboratoire de Physico-Chimie des Matériaux Luminescents (Université Claude Bernard, Lyon, France), si colloca all'interfaccia tra la Biomedicina, la Chimica di Coordinazione e la Fotochimica, alla ricerca di un comune denominatore. L'obiettivo del nostro lavoro è stato quello di sviluppare una metodologia ed un set-up sperimentale per collegare l'esperienza del LaCIC nella sintesi organometallica, con le applicazioni di composti di coordinazione in campo biomedico. Abbiamo scelto tre aree di ricerca in grado di mettere in evidenza la relazione tra "composti di coordinazione", "luce" e "biomedicina": l'applicazione di complessi metallici incapsulati in polimeri o in nanoparticelle di oro e silice per la generazione di ossigeno di singoletto nella Terapia Fotodinamica (Capitoli 3 e 4), l'utilizzo dei processi a trasferimento di energia che coinvolgono i composti di coordinazione per lo studio delle interazioni farmaco-proteina (applicazioni di “sensing”, capitolo 2), l'utilizzo della luminescenza di nanoparticelle contenenti complessi di metalli di transizione nell’imaging cellulare. Le proprietà uniche dei composti metallici, soprattutto la rilevante fotochimica e fotofisica dei composti di metalli di transizione, li rendono idonei per applicazioni in fotomedicina. Capitolo 2 - Applicazione di “sensing” dei composti di coordinazione: interazione farmaco-proteina. Un nuovo complesso di zinco, recentemente sintetizzato presso il LaCIC, ha evidenziato un’interessante attività antiproliferativa in vitro nei confronti di alcune linee cellulari tumorali. Tuttavia, i test in vitro rappresentano solo il primo step per l’applicazione di questo complesso come farmaco antineoplastico; una fase successiva richiede uno studio della sua biodistribuzione, dunque la sua interazione con biomolecole quali l’ Albumina sierica umana, la proteina più abbondante presente nel torrente circolatorio, la quale aumenta la solubilità di farmaci idrofobici nel plasma e ne modula il rilascio a livello cellulare. Grazie alla fluorescenza della proteina, è stato possibile studiarne il fenomeno di quenching della luminescenza, correlandolo all’interazione di legame con il complesso metallico. Inoltre, la "struttura speciale" del composto di coordinazione, la sua luminescenza intrinseca, ha reso possibile lo studio dell’interazione di legame da un’altra prospettiva, giungendo ad una interessante conclusione, che evidenzia l'aspetto multifattoriale del complesso: terapeutico e sensoristico. Capitolo 3 - Processi attivati dalla luce in composti di coordinazione: fotogenerazione di ossigeno di singoletto. La Terapia Fotodinamica (PDT) fa riferimento all’applicazione di luce al fine di ottenere un effetto terapeutico, in particolare fa riferimento alla capacità di fotogenerare 1O2, una specie altamente reattiva (il “vero” agente terapeutico) da una molecola cosiddetta “fotosensibilizzante”. Tra gli effetti terapeutici dell’ 1O2 si pongono in evidenza la terapia antimicrobica e, soprattutto, la terapia antitumorale: in entrambe è preferibilmente richiesto l’utilizzo di fotosensibilizzanti solubili in acqua. I Complessi di Metalli di Transizione (TMC), grazie alle loro “speciali” proprietà fotofisiche, sono fotosensibilizzanti eccellenti, ma per la maggior parte scarsamente idrofilici. Per rendere TMC solubili in acqua si può procedere per esempio inserendoli in un polimero biocompatibile, senza che gli stessi perdino la loro capacità di generare ossigeno di singoletto. Seguendo questo criterio, è stato sintetizzato e caratterizzato il primo esempio di un polimero solubile in acqua legante un complesso di Pt(II) in grado di generare ossigeno di singoletto. Capitolo 4 - Il paradigma “theranostic”: complessi di metalli di transizione e nanoparticelle. Un’altra alternativa per ottenere un fotosensibilizzante solubile in acqua con le “speciali” proprietà dei TMC è di incapsularlo all’interno di nanoparticelle (NPs), le quali stanno sempre più acquisendo una crescente importanza in ambito medico, grazie alla capacità di agire da sistema di rilascio e alla loro bassa tossicità. Su questa base, sono state sintetizzate e caratterizzate un certo numero di NPs aventi un “core” d’oro e una “shell” di silice con intrappolati nella matrice complessi di Ir (III) e Ru (II), aventi la capacità di generare ossigeno di singoletto. Come prova preliminare, un campione di NPs contenenti un complesso di Ru (II), è stato caratterizzato in vitro per valutarne la citotossicità in diverse linee di cellule tumorali, con risultati promettenti. Inoltre, le "speciali" proprietà fotofisiche dei TMC consentono una disattivazione non radiativa degli stati eccitati (fenomeno necessario per la generazione di 1O2 mediante un processo a trasferimento di energia) senza perdere la luminescenza. In virtù di questo, è stato possibile localizzare le NPs fotosensibilizzanti all'interno della cellula mediante microscopia a fluorescenza, rendendo le NPs sintetizzate un nuovo materiale per “theranostic purposes”.University of Calabri

Light-Induced Clusterization of Gold Nanoparticles: A New Photo-Triggered Antibacterial against <i>E. coli</i> Proliferation

Metallic nanoparticles show plasmon resonance phenomena when irradiated with electromagnetic radiation of a suitable wavelength, whose value depends on their composition, size, and shape. The damping of the surface electron oscillation causes a release of heat, which causes a large increase in local temperature. Furthermore, this increase is enhanced when nanoparticle aggregation phenomena occur. Local temperature increase is extensively exploited in photothermal therapy, where light is used to induce cellular damage. To activate the plasmon in the visible range, we synthesized 50 nm diameter spherical gold nanoparticles (AuNP) coated with polyethylene glycol and administered them to an E. coli culture. The experiments were carried out, at different gold nanoparticle concentrations, in the dark and under irradiation. In both cases, the nanoparticles penetrated the bacterial wall, but a different toxic effect was observed; while in the dark we observed an inhibition of bacterial growth of 46%, at the same concentration, under irradiation, we observed a bactericidal effect (99% growth inhibition). Photothermal measurements and SEM observations allowed us to conclude that the extraordinary effect is due to the formation, at low concentrations, of a light-induced cluster of gold nanoparticles, which does not form in the absence of bacteria, leading us to the conclusion that the bacterium wall catalyzes the formation of these clusters which are ultimately responsible for the significant increase in the measured temperature and cause of the bactericidal effect. This photothermal effect is achieved by low-power irradiation and only in the presence of the pathogen: in its absence, the lack of gold nanoparticles clustering does not lead to any phototoxic effect. Therefore, it may represent a proof of concept of an innovative nanoscale pathogen responsive system against bacterial infections