Automated fluorine-18 radiolabeling via an alkyne–azide cycloaddition reaction on a dual peptide-functionalized liposome surface for in vivo PET imaging

A large number of drugs are characterized by limited brain penetrability. The development of advanced delivery systems, such as nanoparticles, may help overcome the blood–brain barrier (BBB) and increase brain accessibility (Spinelli et al., 2019). These systems, which are often engineered to enhance brain accessibility, can mask the physicochemical properties of encapsulated or associated drugs to improve their delivery to the brain parenchyma (Dong, 2018). Nanoparticle functionalization can also be used to develop controlled agents capable of releasing drugs based on the pathological biochemical environment in the target region (Antoniou et al., 2021; Wang and Kohane, 2017). Among different nanoparticles, liposomes show several advantages, including synthetic flexibility, biodegradability, biocompatibility, and low immunogenicity and toxicity. For these reasons, a wide variety of liposome-based formulations have been approved by regulatory agencies as drug delivery systems (Liu et al., 2022). We previously developed an innovative dual-functionalized liposome designed to increase drug availability in brain regions characterized by an inflammatory milieu. In particular, we modified the liposome surface with a peptide derived from the binding domain of apolipoprotein E (mApoE), which is known to increase brain penetration (Bana et al., 2014), and with a metalloproteinase (MMP)-sensitive lipopeptide (MSLP) to confer an MMP-dependent drug release. These liposomes successfully crossed the BBB in vitro and efficiently released an encapsulated fluorescein dye when exposed to MMP-2 and MMP-9, demonstrating their potential for delivering payloads to the brain (Giofrè et al., 2022). Therefore, an automated procedure for the radiolabeling of such functionalized liposomes was developed, using positron emission tomography (PET) imaging to assess whether the BBB penetrability profile of liposomes is maintained in vivo.
https://doi.org/10.3389/fphar.2025.1566257