PHEA-Dox nanoparticles as pH-sensitive model for drug delivery in tumour treatment.

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Abstract

PHEA-Dox nanoparticles as pH-sensitive model for drug delivery in tumour treatment. S. Camporaa, G. Adamoa, N. Maurob, C. Scialabbab, M. Licciardib, G. Giammonab and G. Ghersia.aDipartmento di “Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche” (STEBICEF), Università di Palermo, Viale delle Scienze Ed. 16, 90128 Palermo, Italy.bLaboratory of Biocompatible Polymers, Dipartmento di “Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche” (STEBICEF), Università di Palermo, Via Archirafi, 32 90123 Palermo, Italy.Classical chemotherapeutic applications, using molecules such as doxorubicin (Dox), have side effects due to an unspecific action. In order to obtain a specific release of drugs, PHEA (Poly 2 Hydroxyethyl Aspartamide) nanoparticles (NPs) were synthesized and conjugated with doxorubicin through a pH-sensitive linker namely citraconylamide spacer (PHEA-Dox). Since the tumour microenvironment is more acid (pH 6.4) respect the healthy tissue (pH 7.4), this difference can be used for an intrinsic controlled delivery strategy to induce cancer cells death. In evaluation of this characteristic, “in vitro” experiments were carried out by comparing the PHEA-Dox effect on normal (HB-2) and tumour (MDA-MB-231) human breast cells. Viability assay shows that PHEA-Dox nanoparticles are more cytotoxic to tumour than normal cells. In fact, HB-2 treated for 24h using different concentration of NPs present a viability around 80%; while, in MDA-MB231, there is a reduction of viability dose-dependent to NGs concentration. Moreover, uptake studies were conducted by cytofluorimetric and fluorescence analysis, using a variant of PHEA nanoparticles, labelled with FITC probe (PHEA-FITC-Dox). The cytofluorimetric results reveal that tumour cells present higher intracellular amount of NPs, compared with HB-2 cells, suggesting a faster and greater Doxorubicin release in MDA-MB231. These data are confirmed by fluorescence microscopy, in which there is a significant difference in the PHEA-FITC-Dox localization, over time. The red auto-fluorescence, relative to Dox, appear diffused in cytoplasm of HB2 cells, while it is quickly localized into nuclei of tumour cells. Co-culture experiments show a specific localization of PHEA-Dox nanoparticles in cancer cells after short times of incubation. These data allow us to hypothesize a model of pH-sensitive drug delivery system mediated by PHEA nanoparticles.
Lingua originaleEnglish
Numero di pagine1
Stato di pubblicazionePublished - 2015

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