Albumin microbubbles conjugated with zinc and aluminum phthalocyanine dyes for enhanced photodynamic activity

Roman A Barmin; Elizaveta A Maksimova; Polina G Rudakovskaya; Alexey V Gayer; Evgeny A Shirshin; Kirill S Petrov; Daria A Terentyeva; Olga I Gusliakova; Olga A Sindeeva; Oleg A Klimenko; Roman N Chuprov-Netochin; Alexander A Solovev; Gaoshan Huang; Anastasia V Ryabova; Victor B Loschenov; Dmitry A Gorin

doi:10.1016/j.colsurfb.2022.112856

Albumin microbubbles conjugated with zinc and aluminum phthalocyanine dyes for enhanced photodynamic activity

Colloids Surf B Biointerfaces. 2022 Nov:219:112856. doi: 10.1016/j.colsurfb.2022.112856. Epub 2022 Sep 17.

Authors

Roman A Barmin¹, Elizaveta A Maksimova², Polina G Rudakovskaya², Alexey V Gayer³, Evgeny A Shirshin⁴, Kirill S Petrov⁵, Daria A Terentyeva⁶, Olga I Gusliakova⁷, Olga A Sindeeva², Oleg A Klimenko⁸, Roman N Chuprov-Netochin⁹, Alexander A Solovev¹⁰, Gaoshan Huang¹⁰, Anastasia V Ryabova¹¹, Victor B Loschenov¹², Dmitry A Gorin¹³

Affiliations

¹ Skolkovo Institute of Science and Technology, 3 Nobelya Str., Moscow 121205, Russia. Electronic address: Roman.Barmin@skoltech.ru.
² Skolkovo Institute of Science and Technology, 3 Nobelya Str., Moscow 121205, Russia.
³ Lomonosov Moscow State University, 1/2 Leninskie Gory, Moscow 119991, Russia.
⁴ Lomonosov Moscow State University, 1/2 Leninskie Gory, Moscow 119991, Russia; Institute of Spectroscopy of the Russian Academy of Sciences, 5 Fizicheskaya Str., Troitsk, Moscow 108840, Russia; Institute for Regenerative Medicine, Sechenov First Moscow State Medical University, Trubetskaya 8-2, Moscow 119048, Russia.
⁵ Hadassah Medical Center, 46 Bolshoy Boulevard, Moscow 121205, Russia.
⁶ Department of Fine Organic Synthesis and Chemistry of Dyes, Dmitry Mendeleev University of Chemical Technology of Russia, Moscow 125047, Russia.
⁷ Remote Controlled Theranostic Systems Lab, Saratov State University, 83 Astrakhanskaya Str., Saratov 410012, Russia.
⁸ Skolkovo Institute of Science and Technology, 3 Nobelya Str., Moscow 121205, Russia; P.N. Lebedev Physical Institute of the Russian Academy of Sciences, Moscow 119991, Russia.
⁹ School of Biological and Medical Physics, Moscow Institute of Physics and Technology, Dolgoprudny 141700, Russia.
¹⁰ Fudan University, Shanghai 200433, People's Republic of China.
¹¹ Prokhorov General Physics Institute of the Russian Academy of Sciences, Moscow 119991, Russia.
¹² Prokhorov General Physics Institute of the Russian Academy of Sciences, Moscow 119991, Russia; National Research Nuclear University MEPhI (Moscow Engineering Physics Institute MEPhI), Kashirskoye shosse 31, Moscow 115409, Russia.
¹³ Skolkovo Institute of Science and Technology, 3 Nobelya Str., Moscow 121205, Russia. Electronic address: D.Gorin@skoltech.ru.

PMID: 36150237
DOI: 10.1016/j.colsurfb.2022.112856

Abstract

Gas-liquid interfaces are reaching a particular interest in biomedicine. Microbubbles, ultrasound contrast agents of clinical routine, gained increasing attention as theranostic platforms due to the preserved acoustic response, drug conjugation capabilities, and applicability in biological barrier opening. A combination of microbubbles and photodynamic therapy agents can enhance the photodynamic effect, yet the evaluation of agent conjugation on microbubble stabilization and photodynamic effect is needed. Hence, two commercially available phthalocyanine photosensitizers - Holosens® (ZnPc) and Photosens® (AlPc) - were coupled with bovine serum albumin before microbubble synthesis. We demonstrated an albumin: phthalocyanine ratio of 1:1 and covalent attachment for ZnPc, a ratio of 1:3 with electrostatic binding for AlPc. Submicron-sized microbubbles (air- and SF₆- filled) had a diameter of 0.8 µm. Albumin-phthalocyanine conjugates increased the microbubble concentration and shelf-life stability compared to plain ones. We hypothesized that phthalocyanine fluorescence lifetime values decreased after conjugation with microbubbles due to narrow distance between conjugates in the shell. Agents based on AlPc demonstrated higher photodynamic activity than agents based on ZnPc, and microbubbles preserved acoustic stability in human blood plasma. The biodistribution of AlPc-conjugated microbubbles was evaluated. We conclude that our microbubble platforms demonstrate greater photodynamic activity and prolonged stability for further applications in photodynamic therapy.

Keywords: Albumin; Aluminum phthalocyanine; Microbubbles; Photodynamic effect; Zinc phthalocyanine.