Niosomes Functionalized with a Synthetic Carbohydrate Binding Agent for Mannose-Targeted Doxorubicin Delivery
Nastassja Burrini,
Mario D’Ambrosio,
Matteo Gentili,
Roberta Giaquinto,
Veronica Settimelli,
Cristina Luceri,
Marzia Cirri,
Oscar Francesconi
Affiliations
Nastassja Burrini
Department of Chemistry “Ugo Schiff” (DICUS), Università degli Studi di Firenze, Polo Scientifico e Tecnologico, 50019 Sesto Fiorentino, Italy
Mario D’Ambrosio
Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), Section of Pharmacology and Toxicology, Università degli Studi di Firenze, Viale Pieraccini 6, 50139 Firenze, Italy
Matteo Gentili
Department of Chemistry “Ugo Schiff” (DICUS), Università degli Studi di Firenze, Polo Scientifico e Tecnologico, 50019 Sesto Fiorentino, Italy
Roberta Giaquinto
Department of Chemistry “Ugo Schiff” (DICUS), Università degli Studi di Firenze, Polo Scientifico e Tecnologico, 50019 Sesto Fiorentino, Italy
Veronica Settimelli
Department of Chemistry “Ugo Schiff” (DICUS), Università degli Studi di Firenze, Polo Scientifico e Tecnologico, 50019 Sesto Fiorentino, Italy
Cristina Luceri
Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), Section of Pharmacology and Toxicology, Università degli Studi di Firenze, Viale Pieraccini 6, 50139 Firenze, Italy
Marzia Cirri
Department of Chemistry “Ugo Schiff” (DICUS), Università degli Studi di Firenze, Polo Scientifico e Tecnologico, 50019 Sesto Fiorentino, Italy
Oscar Francesconi
Department of Chemistry “Ugo Schiff” (DICUS), Università degli Studi di Firenze, Polo Scientifico e Tecnologico, 50019 Sesto Fiorentino, Italy
Niosomes are a potential tool for the development of active targeted drug delivery systems (DDS) for cancer therapy because of their excellent behaviour in encapsulating antitumorals and the possibility to easily functionalise their surface with targeting agents. Recently, some of us developed a synthetic carbohydrate binding agent (CBA) able to target the mannosidic residues of high-mannose-type glycans overexpressed on the surface of several cancer cell lines, promoting their apoptosis. In this article, we modified the structure of this mannose receptor to obtain an amphiphilic analogue suitable for the functionalization of doxorubicin-based niosomes. Several niosomal formulations and preparation methods were investigated deeply to finally obtain functionalized niosomes suitable for parental administration, which were stable for over six months and able to encapsulate up to 85% of doxorubicin (DOXO). In vitro studies, carried out towards triple-negative cancer cells (MDA-MB231), overexpressing high-mannose-type glycans, showed a cytotoxic activity comparable to that of DOXO but with an appreciable increment in apoptosis given by the CBA. Moreover, niosomal formulation was observed to reduce doxorubicin-induced cytotoxicity towards normal cell lines of rat cardiomyocytes (H9C2). This study is propaedeutic to further in vivo investigations that can aim to shed light on the antitumoral activity and pharmacokinetics of the developed active targeted DDS.
