HER2-specific liposomes loaded with proteinaceous BRET pair as a promising tool for targeted self-excited photodynamic therapy.

Autor: Shramova EI; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Academy of science, 16/10 Miklukho-Maklaya Street, Moscow 117997, Russia., Filimonova VP; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Academy of science, 16/10 Miklukho-Maklaya Street, Moscow 117997, Russia., Frolova AY; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Academy of science, 16/10 Miklukho-Maklaya Street, Moscow 117997, Russia., Pichkur EB; Peter the Great St. Petersburg Polytechnic University, Politehnicheskaya 29, 195251 St. Petersburg, Russia., Fedotov VR; Peter the Great St. Petersburg Polytechnic University, Politehnicheskaya 29, 195251 St. Petersburg, Russia., Konevega AL; Peter the Great St. Petersburg Polytechnic University, Politehnicheskaya 29, 195251 St. Petersburg, Russia., Deyev SM; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Academy of science, 16/10 Miklukho-Maklaya Street, Moscow 117997, Russia; 'Biomarker' Research Laboratory, Institute of Fundamental Medicine and Biology, Kazan Federal University, 18 Kremlyovskaya St., Kazan 420008, Russia; Sechenov First Moscow State Medical University (Sechenov University), 119991, Moscow, Russia., Proshkina GM; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Academy of science, 16/10 Miklukho-Maklaya Street, Moscow 117997, Russia. Electronic address: gmb@ibch.ru.
Jazyk: angličtina
Zdroj: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V [Eur J Pharm Biopharm] 2023 Dec; Vol. 193, pp. 208-217. Date of Electronic Publication: 2023 Nov 11.
DOI: 10.1016/j.ejpb.2023.11.008
Abstrakt: Photodynamic therapy (PDT) for deep-seated tumors is still challenging due to the limited penetration of visible light through tissues. To resolve this limitation, systems based on bioluminescence resonance energy transfer (BRET), that do not require an external light source are proposed. Herein, for BRET-activated PDT we developed proteinaceous BRET-pair consisting of luciferase NanoLuc, which acts as energy donor upon addition of luciferase specific substrate furimazine, and phototoxic protein SOPP3 as a photosensitizer. We have shown that hybrid protein NanoLuc-SOPP3 is an excellent BRET pair with BRET ratio of 1.12. Targeted delivery of NanoLuc-SOPP3 BRET pair via tumor-specific small liposomes (∼100 nm) to tumors overexpressing the HER2-receptor (human epidermal growth factor receptor 2) was demonstrated in vitro and in vivo. The proposed BRET-activated system has been shown to significantly suppress tumor growth in a model of subcutaneous and, more importantly, deep-seated tumor model. Taking into account the in vivo efficiency of proposed BRET-activated system, we believe that it has great potential for depth-independent PDT and can significantly broaden the application of PDT in the clinic.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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