P V Ostroverkhov1, A S Semkina2, V A Naumenko3, E A Plotnikova4, P A Melnikov2, T O Abakumova5, R I Yakubovskaya4, A F Mironov6, S S Vodopyanov7, A M Abakumov8, A G Majouga9, M A Grin10, V P Chekhonin11, M A Abakumov12. 1. Russian Technological University (MIREA), 86 Vernadsky Avenue, 119571 Moscow, Russia. Electronic address: mrp_ost@mail.ru. 2. Pirogov Russian National Research Medical University, Ostrovitianov Str. 1, 117997 Moscow, Russia. 3. National Research Technological University "MISiS", Biomedical Nanomaterials, Leninskiy Prospekt 4, 119049 Moscow, Russia. 4. FSBI NMRRC of the Ministry of Health of the Russian Federation, 2-Y Botkinskiy Proyezd 3, 125284 Moscow, Russia. 5. Skolkovo Institute of Science and Technology, Nobelya Ulitsa 3, 121205 Moscow, Russia. 6. Russian Technological University (MIREA), 86 Vernadsky Avenue, 119571 Moscow, Russia. Electronic address: mironov@mitht.ru. 7. National Research Technological University "MISiS", Biomedical Nanomaterials, Leninskiy Prospekt 4, 119049 Moscow, Russia. Electronic address: stepan.vodopianov@yandex.ru. 8. Skolkovo Institute of Science and Technology, Nobelya Ulitsa 3, 121205 Moscow, Russia. Electronic address: A.Abakumov@skoltech.ru. 9. Dmitry Mendeleev University of Chemical Technology of Russia, Miusskaya sq., 9, 125047 Moscow, Russia. 10. Russian Technological University (MIREA), 86 Vernadsky Avenue, 119571 Moscow, Russia. Electronic address: michael_grin@mail.ru. 11. Pirogov Russian National Research Medical University, Ostrovitianov Str. 1, 117997 Moscow, Russia. Electronic address: chekhoninnew@yandex.ru. 12. Pirogov Russian National Research Medical University, Ostrovitianov Str. 1, 117997 Moscow, Russia; National Research Technological University "MISiS", Biomedical Nanomaterials, Leninskiy Prospekt 4, 119049 Moscow, Russia. Electronic address: abakumov_ma@rsmu.ru.
Abstract
HYPOTHESIS: Hydrophobic bacteriochlorin based photosensitizer (PS) can be effectively immobilized on MNP covered by human serum albumin (HSA). PS loading into MNP protein shell allows solubilizing PS in water solution without altering its photodynamic activity. MNP@PS can serve as diagnostic tool for tracking PS delivery to tumor tissues by MRI. EXPERIMENTS: Immobilization on MNP-HSA-PEG was performed by adding PS solution in organic solvents with further purification. MNP@PS were characterized by DLS, HAADF STEM and AFM. Absorbance and fluorescence measurements were used to assess PS photophysical properties before and after immobilization. MNP@PS internalization into CT26 cells was investigated by confocal microscopy in vitro and MRI/IVIS were used for tracking MNP@PS delivery to tumors in vivo. FINDINGS: MNP@PS complexes were stable in water solution and retained PS photophysical activity. The length of side chain affected MNP@PS size, loading capacity and cell internalization. In vitro testing demonstrated MNP@PS delivery to cancer cells followed by photoinduced toxicity. In vivo studies confirmed that as-synthetized complexes can be used for MRI tracking over drug accumulation in tumors.
HYPOTHESIS: Hydrophobic bacteriochlorin based photosensitizer (PS) can be effectively immobilized on MNP covered by humanserum albumin (HSA). PS loading into MNP protein shell allows solubilizing PS in water solution without altering its photodynamic activity. MNP@PS can serve as diagnostic tool for tracking PS delivery to tumor tissues by MRI. EXPERIMENTS: Immobilization on MNP-HSA-PEG was performed by adding PS solution in organic solvents with further purification. MNP@PS were characterized by DLS, HAADF STEM and AFM. Absorbance and fluorescence measurements were used to assess PS photophysical properties before and after immobilization. MNP@PS internalization into CT26 cells was investigated by confocal microscopy in vitro and MRI/IVIS were used for tracking MNP@PS delivery to tumors in vivo. FINDINGS: MNP@PS complexes were stable in water solution and retained PS photophysical activity. The length of side chain affected MNP@PS size, loading capacity and cell internalization. In vitro testing demonstrated MNP@PS delivery to cancer cells followed by photoinduced toxicity. In vivo studies confirmed that as-synthetized complexes can be used for MRI tracking over drug accumulation in tumors.