Synthesis and Characterization of Multifunctional Nanovesicles Composed of POPC Lipid Molecules for Nuclear Imaging.

Debora Petroni,Irene Russo Krauss,Luigi Paduano,Luca Menichetti,Daniela Montesarchio,Domenico Cavasso,Claudia Riccardi

doi:10.3390/molecules26216591

Abstract

The integration of nuclear imaging analysis with nanomedicine has tremendously grown and represents a valid and powerful tool for the development and clinical translation of drug delivery systems. Among the various types of nanostructures used as drug carriers, nanovesicles represent intriguing platforms due to their capability to entrap both lipophilic and hydrophilic agents, and their well-known biocompatibility and biodegradability. In this respect, here we present the development of a labelling procedure of POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine)-based liposomes incorporating an ad hoc designed lipophilic NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid) analogue, derivatized with an oleic acid residue, able to bind the positron emitter gallium-68(III). Based on POPC features, the optimal conditions for liposome labelling were studied with the aim of optimizing the Ga(III) incorporation and obtaining a significant radiochemical yield. The data presented in this work demonstrate the feasibility of the labelling procedure on POPC liposomes co-formulated with the ad hoc designed NOTA analogue. We thus provided a critical insight into the practical aspects of the development of vesicles for theranostic approaches, which in principle can be extended to other nanosystems exploiting a variety of bioconjugation protocols.

Highlights

Among the various types of known drug carriers, the nanostructured ones—by far the most investigated delivery systems [1]—find application in the radiopharmaceutical field
To expand the potential and applicability of these systems, in this work, we describe a new synthesis and labelling approach starting from a POPC liposome
monometho xytrityl (MMT) was introduced at one end of 1,2-diaminoethane

Summary

Introduction

Among the various types of known drug carriers, the nanostructured ones (micelles, dendrimers, etc.)—by far the most investigated delivery systems [1]—find application in the radiopharmaceutical field. Nuclear imaging techniques are frequently used to study new drug delivery systems because of their unique capacity to perform dynamic studies [2,3]. Liposomes are a notable exception in this context: their limited use as radiopharmaceuticals is mainly related to their intrinsic properties and peculiar physical and chemical stability. The different interplay between hydrophobic and hydrophilic layers in their microstructure makes labelling of liposomes a real challenge; the control of the labelling efficiency and stability of the radiolabelled product is a critical issue. The aim of this work is the design and preparation of stable liposomal formulations suitable for positron emission tomography (PET) imaging

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Conclusion