Niosomes Functionalized with a Synthetic Carbohydrate Binding Agent for Mannose-Targeted Doxorubicin Delivery

Abstract

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.

Towards Biomimetic Recognition of Glycans by Synthetic Receptors

“…Moreover, the ability of mannose‐binding concanavalin A (ConA) to bind cells overexpressing mannosides was attenuated in the presence of ( R )‐ 7 and ( S )‐ 7 . More recently, receptor ( R )‐ 7 has been used to develop functionalized niosomes for mannose‐targeted doxorubicin delivery [75] . In vitro studies towards triple‐negative cancer cells (MDA‐MB‐231), overexpressing high‐mannose type glycans, showed for the functionalized niosomes a cytotoxic activity comparable to free ( R )‐ 7 demonstrating the correct presentation of the CBA in niosomes, and for functionalized niosomes loaded with doxorubicin a cytotoxic activity comparable to free doxorubicin but with an appreciable increment in apoptosis given by the CBA.…”