title: Nanoassemblies based on non-ionic amphiphilic cyclodextrin hosting Zn(II)-phthalocyanine and docetaxel: Design, physicochemical properties and intracellular effects.
abstract: The combination of conventional anticancer therapy with other treatment modalities such as photodynamic therapy (PDT) is paving the way to novel more effective treatment of solid tumors via light exposure. With this idea in mind, in this paper, nanoparticles (NPs) based on Heptakis (2-oligo(ethyleneoxide)-6-hexadecylthio-)-β-CD (SC16OH) for dual delivery of Zinc-Phthalocyanine (ZnPc) and Docetaxel (DTX) were developed pointing to their potential application as nanomedicine for the combined photodynamic and chemo-therapy of solid tumors. NPs prepared by the emulsion-solvent evaporation technique displayed a hydrodynamic diameter of ≅ 200nm, a negative zeta potential (≅ -27mV) and a satisfactory entrapment efficiency of both drugs at a specific mass ratio. On these bases, NPs containing DTX and ZnPc with theoretical loading of 5% and 0.2% respectively (ZnPc/DTX5-NPs) were selected for further investigations. The allocation of ZnPc and DTX into the colloid was investigated by complementary spectroscopic techniques. In particular, fluorescence emission studies showed the entrapment of ZnPc as a monomer in the carrier, with a low tendency to self-aggregate and consequently a fairly high propensity to photogenerate singlet oxygen. The interaction of SC16OH with DTX, co-entrapped with ZnPc, was elucidated by (1)H NMR and 2D ROESY, which suggested the presence of the chemotherapeutic in the hydrophobic portion of SC16OH. ZnPc/DTX5-NPs were fairly stable in different biological relevant media within 24h. Finally, in vitro potential of the nanoassembly was evaluated in HeLa cancer cells by cell viability exploring both effects of DTX and ZnPc. Overall, results suggest the suitability of NPs based on SC16OH for delivering a combination of DTX with ZnPc to cancer cells, thus inducing photodynamic and antimitotic effects.
authors.affiliation: Dipartimento di Farmacia, Università di Napoli Federico II, Via Domenico Montesano 49, 80131 Napoli, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Conte
authors.affiliation: Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche ed Ambientali, Università di Messina, V.le F. Stagno D'Alcontres 31, 98166 Messina, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Scala
authors.affiliation: Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche ed Ambientali, Università di Messina, V.le F. Stagno D'Alcontres 31, 98166 Messina, Italy.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Siracusano
authors.affiliation: Consiglio Nazionale delle Ricerche CNR-ISMN c/o Dip. di Scienze Chimiche, Biologiche, Farmaceutiche ed Ambientali dell'Università di Messina, V.le F. Stagno D'Alcontres 31, 98166 Messina, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Sortino
authors.affiliation: Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche ed Ambientali, Università di Messina, V.le F. Stagno D'Alcontres 31, 98166 Messina, Italy.
authors.forename: Rosamaria
authors.initials: R
authors.lastname: Pennisi
authors.affiliation: Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche ed Ambientali, Università di Messina, V.le F. Stagno D'Alcontres 31, 98166 Messina, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Piperno
authors.affiliation: Dipartimento di Farmacia, Università di Napoli Federico II, Via Domenico Montesano 49, 80131 Napoli, Italy.
authors.forename: Agnese
authors.initials: A
authors.lastname: Miro
authors.affiliation: Dipartimento di Farmacia, Università di Napoli Federico II, Via Domenico Montesano 49, 80131 Napoli, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ungaro
authors.affiliation: Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche ed Ambientali, Università di Messina, V.le F. Stagno D'Alcontres 31, 98166 Messina, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Sciortino
authors.affiliation: Dipartimento di Farmacia, Università di Napoli Federico II, Via Domenico Montesano 49, 80131 Napoli, Italy. Electronic address: quaglia@unina.it.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Quaglia
authors.affiliation: Consiglio Nazionale delle Ricerche CNR-ISMN c/o Dip. di Scienze Chimiche, Biologiche, Farmaceutiche ed Ambientali dell'Università di Messina, V.le F. Stagno D'Alcontres 31, 98166 Messina, Italy. Electronic address: antonino.mazzaglia@ismn.cnr.it.
authors.forename: Antonino
authors.initials: A
authors.lastname: Mazzaglia
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D003505:Cyclodextrins / Q000737:chemistry*; D000077143:Docetaxel; D006367:HeLa Cells; D006801:Humans; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology; D054833:Isoindoles; D009942:Organometallic Compounds / Q000737:chemistry* / Q000494:pharmacology; D013501:Surface-Active Agents / Q000737:chemistry*; D043823:Taxoids / Q000737:chemistry* / Q000494:pharmacology; D017967:Zinc Compounds
chemical_list: D003505:Cyclodextrins; D007211:Indoles; D054833:Isoindoles; D009942:Organometallic Compounds; D013501:Surface-Active Agents; D043823:Taxoids; D017967:Zinc Compounds; C052159:Zn(II)-phthalocyanine; D000077143:Docetaxel
keywords: Amphiphilic cyclodextrin; Co-delivery; Combined anti-cancer therapy; Docetaxel; Zn(II)-phthalocyanine