title: Nanoparticle-mediated delivery of suicide genes in cancer therapy.
abstract: Conventional chemotherapeutics have been employed in cancer treatment for decades due to their efficacy in killing the malignant cells, but the other side of the coin showed off-target effects, onset of drug resistance and recurrences. To overcome these limitations, different approaches have been investigated and suicide gene therapy has emerged as a promising alternative. This approach consists in the introduction of genetic materials into cancerous cells or the surrounding tissue to cause cell death or retard the growth of the tumor mass. Despite promising results obtained both in vitro and in vivo, this innovative approach has been limited, for long time, to the treatment of localized tumors, due to the suboptimal efficiency in introducing suicide genes into cancer cells. Nanoparticles represent a valuable non-viral delivery system to protect drugs in the bloodstream, to improve biodistribution, and to limit side effects by achieving target selectivity through surface ligands. In this scenario, the real potential of suicide genes can be translated into clinically viable treatments for patients. In the present review, we summarize the recent advances of inorganic nanoparticles as non-viral vectors in terms of therapeutic efficacy, targeting capacity and safety issues. We describe the main suicide genes currently used in therapy, with particular emphasis on toxin-encoding genes of bacterial and plant origin. In addition, we discuss the relevance of molecular targeting and tumor-restricted expression to improve treatment specificity to cancer tissue. Finally, we analyze the main clinical applications, limitations and future perspectives of suicide gene therapy.
authors.affiliation: Università Vita-Salute San Raffaele, Milano, I-20132, Italy; Istituto di Ricerca Urologica, Divisione di Oncologia Sperimentale, IRCCS Ospedale San Raffaele, Via Olgettina 60, 20132, Milan, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Vago
authors.affiliation: Università degli Studi di Milano-Bicocca, NanoBioLab, Dipartimento di Biotecnologie e Bioscienze, Piazza Della Scienza 2, 20126 Milan, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Collico
authors.affiliation: Università degli Studi di Milano-Bicocca, NanoBioLab, Dipartimento di Biotecnologie e Bioscienze, Piazza Della Scienza 2, 20126 Milan, Italy; Istituto di Ricerca Urologica, Divisione di Oncologia Sperimentale, IRCCS Ospedale San Raffaele, Via Olgettina 60, 20132, Milan, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Zuppone
authors.affiliation: Università degli Studi di Milano-Bicocca, NanoBioLab, Dipartimento di Biotecnologie e Bioscienze, Piazza Della Scienza 2, 20126 Milan, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Prosperi
authors.affiliation: Università degli Studi di Milano-Bicocca, NanoBioLab, Dipartimento di Biotecnologie e Bioscienze, Piazza Della Scienza 2, 20126 Milan, Italy. Electronic address: miriam.colombo@unimib.it.
authors.forename: Miriam
authors.initials: M
authors.lastname: Colombo
mesh_terms: D000818:Animals; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D053758:Nanoparticles / Q000008:administration & dosage*; D009369:Neoplasms / Q000235:genetics / Q000628:therapy*
keywords: Active targeting; Cancer treatment; Nanovectors; Non-viral gene delivery; Suicide therapy; Toxins