Preparation of Benzothiazolyl-Decorated Nanoliposomes

Abstract

Amyloid β (Aβ) species are considered as potential targets for the development of diagnostics/therapeutics towards Alzheimer’s disease (AD). Nanoliposomes which are decorated with molecules having high affinity for Aβ species may be considered as potential carriers for AD theragnostics. Herein, benzothiazolyl (BTH) decorated nanoliposomes were prepared for the first time, after synthesis of a lipidic BTH derivative (lipid-BTH). The synthetic pathway included acylation of bis(2-aminophenyl) disulfide with palmitic acid or palmitoyl chloride and subsequent reduction of the oxidized dithiol derivative. The liberated thiols were able to cyclize to the corresponding benzothiazolyl derivatives only after acidification of the reaction mixture. Each step of the procedure was monitored by HPLC analysis in order to identify all the important parameters for the formation of the BTH-group. Finally, the optimal methodology was identified, and was applied for the synthesis of the lipid-BTH derivative. BTH-decorated nanoliposomes were then prepared and characterized for physicochemical properties (size distribution, surface charge, physical stability, and membrane integrity during incubation in presence of buffer and plasma proteins). Pegylated BTH-nanoliposomes were demonstrated to have high integrity in the presence of proteins (in comparison to non-peglated ones) justifying their further exploitation as potential theragnostic systems for AD.

Amyloid Oligomers: A Joint Experimental/Computational Perspective on Alzheimer’s Disease, Parkinson’s Disease, Type II Diabetes, and Amyotrophic Lateral Sclerosis

“…928 Nanoliposomes decorated with Aβ binding surface containing benzothiazolyl are proposed to be an effective therapeutic systems for AD treatment. 929 For other peptide-based inhibitors, readers are referred to a recent review 930 and recent articles. [931][932][933]…”

“…Cationic fluorescent conjugated polymer nanoparticles are shown to inhibit Aβ aggregation . Nanoliposomes decorated with Aβ binding surface containing benzothiazolyl are proposed to be an effective therapeutic systems for AD treatment . For other peptide-based inhibitors, readers are referred to a recent review and recent articles. − …”

<p>Innovative Therapies and Nanomedicine Applications for the Treatment of Alzheimer’s Disease: A State-of-the-Art (2017–2020)</p>

“…Despite they showed only in vitro studies, also in this case the results seem promising for a theragnostic approach. 128 Overall, besides the first exciting theragnostics examples were mostly applied in oncology, emerging possibilities are continuously increasing and seem to be likely suitable also for neurodegenerative disorders.…”

Liposomes Decorated with 2-(4′-Aminophenyl)benzothiazole Effectively Inhibit Aβ1–42 Fibril Formation and Exhibit in Vitro Brain-Targeting Potential

“…50 In fact, benzothiazole derivatives were never considered up-to-date for the construction of potential therapeutic nanosystems, via conjugation/immobilization on the surface of NPs. The only benzothiazolyl-decorated NP that is reported describes the development of unsubstituted 2benzothiazole liposomes, 51 but their interaction with amyloid species and their potential to be transported across the BBB were not evaluated.…”

“…Herein, taking into consideration the capability of benzothiazoles to interact with Αβ42 and the known potential of nanotechnologies to enhance the function of active compounds that are immobilized on their surface due to multivalency, we study for the first time, the activity of benzothiazolyl liposomes toward Αβ species. In more detail, we compare two different types of benzothiazolyl liposomes for their potential to interact with Aβ42 and inhibit Aβ42 aggregation: (i) unsubstituted 2benzothiazole (BTH)-decorated liposomes (BTH-LIP), which were formed as previously reported, 51 and (ii) 2-arylsubstituted benzothiazole (AP-BTH)-decorated liposomes (AP-BTH-LIP), which were formed after establishing an appropriate methodology for the synthesis of stable vesicles.…”