The cytotoxic cisplatin effect is exploited in the treatment of solid tumors since four decades. Despite its success, cisplatin has several disadvantages including nephrotoxicity, neurotoxicity, ototoxicity, nausea and vomiting. Therefore, many efforts have been devoted to reduce these effects developing new platinum complexes1 and advanced systems for drug targeting. Innovative approaches, that could overcome platinum resistance and adverse side effects, are focused on delivering cytotoxic platinum complexes through an active targeting. Our purpose is the development of tools functionalized by octreotide bioactive peptide able to recognize somatostatin receptors overexpressed in a wide number of solid tumors3. At the beginning PtCl2-N-ethylglycine complex was covalently anchored to the N-terminus of octreotide peptide spaced with two ethoxilic groups in order to increase hydrophilic behaviour. In a second approach liposomal aggregates have been designed and formulated by co-assembling amphiphilic monomers: a phospholipid that drives liposome formulation and a second synthetic monomer containing the octreotide. The platinum drug was introduced by adding in the liposome formulation a third amphiphilic monomer containing the same PtCl2-N-ethylglycine complex covalently bound to a lysine residue bearing a lipophilic moiety and a PEG 1500 chain. Alternatively, novel procedure were developed in order to load cisplatin in the aqueous liposome inner compartment. Liposomes were structurally characterized by dynamic light scattering (DLS) measurements. Data indicate the formation of stable aggregates with size and shape in the right range for in vivo applications. Biological assays on cells overexpressing somatostatin receptors (SSTR2) will be reported.
Pt(II) complexes delivered by Octreotide peptide conjugate or peptide decorated liposome / Tesauro, Diego; Ringhieri, Paola; A., Pannunzio; M., Coluccia; Morelli, Giancarlo. - (2013), pp. 56-56. (Intervento presentato al convegno Thirteenth workshop on PharmacoBioMetallics tenutosi a Catania nel 25-26 ottobre).
Pt(II) complexes delivered by Octreotide peptide conjugate or peptide decorated liposome
TESAURO, DIEGO;RINGHIERI, PAOLA;MORELLI, GIANCARLO
2013
Abstract
The cytotoxic cisplatin effect is exploited in the treatment of solid tumors since four decades. Despite its success, cisplatin has several disadvantages including nephrotoxicity, neurotoxicity, ototoxicity, nausea and vomiting. Therefore, many efforts have been devoted to reduce these effects developing new platinum complexes1 and advanced systems for drug targeting. Innovative approaches, that could overcome platinum resistance and adverse side effects, are focused on delivering cytotoxic platinum complexes through an active targeting. Our purpose is the development of tools functionalized by octreotide bioactive peptide able to recognize somatostatin receptors overexpressed in a wide number of solid tumors3. At the beginning PtCl2-N-ethylglycine complex was covalently anchored to the N-terminus of octreotide peptide spaced with two ethoxilic groups in order to increase hydrophilic behaviour. In a second approach liposomal aggregates have been designed and formulated by co-assembling amphiphilic monomers: a phospholipid that drives liposome formulation and a second synthetic monomer containing the octreotide. The platinum drug was introduced by adding in the liposome formulation a third amphiphilic monomer containing the same PtCl2-N-ethylglycine complex covalently bound to a lysine residue bearing a lipophilic moiety and a PEG 1500 chain. Alternatively, novel procedure were developed in order to load cisplatin in the aqueous liposome inner compartment. Liposomes were structurally characterized by dynamic light scattering (DLS) measurements. Data indicate the formation of stable aggregates with size and shape in the right range for in vivo applications. Biological assays on cells overexpressing somatostatin receptors (SSTR2) will be reported.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.