Taxanes are highly effective chemotherapeutic drugs against proliferating cancer and an established option in the standard treatment of ovarian and breast cancer. However, treatment with paclitaxel is associated with severe side effects, including sensory axonal neuropathy, and its poor solubility in water complicates its formulation. In this paper we report the in vitro and in vivo activity of a new form of paclitaxel, modified for conjugation with a tumor-selective tetrabranched peptide carrier (NT4). NT4 selectively targets tumor cells by binding to membrane sulfated glycosaminoglycans (GAG) and to endocytic receptors, like LRP1 and LRP6, which are established tumor markers. Biological activity of NT4-paclitaxel was tested in vitro on MDA-MB 231 and SKOV-3 cell lines, representing breast and ovarian cancer, respectively, and in vivo in an orthotopic mouse model of human breast cancer. Using in vivo bioluminescence imaging, we found that conjugation of paclitaxel with the NT4 peptide led to increased therapeutic activity of the drug in vivo. NT4-paclitaxel induced tumor regression, whereas treatment with unconjugated paclitaxel only produced a reduction in tumor growth. Moreover, unlike paclitaxel, NT4-paclitaxel is very hydrophilic, which may improve its pharmacokinetic profile and allow the use of less toxic dilution buffers, further decreasing its general chemotherapic toxicity.

Brunetti, J., Pillozzi, S., Falciani, C., Depau, L., Tenori, E., Scali, S., et al. (2015). Tumor-selective peptide-carrier delivery of Paclitaxel increases in vivo activity of the drug. SCIENTIFIC REPORTS, 5, 1-9 [10.1038/srep17736].

Tumor-selective peptide-carrier delivery of Paclitaxel increases in vivo activity of the drug

BRUNETTI, JLENIA;FALCIANI, CHIARA;DEPAU, LORENZO;SCALI, SILVIA;LOZZI, LUISA;PINI, ALESSANDRO;BRACCI, LUISA
2015-01-01

Abstract

Taxanes are highly effective chemotherapeutic drugs against proliferating cancer and an established option in the standard treatment of ovarian and breast cancer. However, treatment with paclitaxel is associated with severe side effects, including sensory axonal neuropathy, and its poor solubility in water complicates its formulation. In this paper we report the in vitro and in vivo activity of a new form of paclitaxel, modified for conjugation with a tumor-selective tetrabranched peptide carrier (NT4). NT4 selectively targets tumor cells by binding to membrane sulfated glycosaminoglycans (GAG) and to endocytic receptors, like LRP1 and LRP6, which are established tumor markers. Biological activity of NT4-paclitaxel was tested in vitro on MDA-MB 231 and SKOV-3 cell lines, representing breast and ovarian cancer, respectively, and in vivo in an orthotopic mouse model of human breast cancer. Using in vivo bioluminescence imaging, we found that conjugation of paclitaxel with the NT4 peptide led to increased therapeutic activity of the drug in vivo. NT4-paclitaxel induced tumor regression, whereas treatment with unconjugated paclitaxel only produced a reduction in tumor growth. Moreover, unlike paclitaxel, NT4-paclitaxel is very hydrophilic, which may improve its pharmacokinetic profile and allow the use of less toxic dilution buffers, further decreasing its general chemotherapic toxicity.
2015
Brunetti, J., Pillozzi, S., Falciani, C., Depau, L., Tenori, E., Scali, S., et al. (2015). Tumor-selective peptide-carrier delivery of Paclitaxel increases in vivo activity of the drug. SCIENTIFIC REPORTS, 5, 1-9 [10.1038/srep17736].
File in questo prodotto:
File Dimensione Formato  
Articolo Brunetti et al., 2015, Scientific Reports.pdf

accesso aperto

Tipologia: PDF editoriale
Licenza: Creative commons
Dimensione 893.44 kB
Formato Adobe PDF
893.44 kB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/982376