Combined Fluorescence and Optoacoustic Imaging for Monitoring Treatments against CT26 Tumors with Photoactivatable Liposomes

Ilya Turchin; Shazia Bano; Mikhail Kirillin; Anna Orlova; Valeriya Perekatova; Vladimir Plekhanov; Ekaterina Sergeeva; Daria Kurakina; Aleksandr Khilov; Alexey Kurnikov; Pavel Subochev; Marina Shirmanova; Anastasiya Komarova; Diana Yuzhakova; Alena Gavrina; Srivalleesha Mallidi; Tayyaba Hasan

doi:10.3390/cancers14010197

Combined Fluorescence and Optoacoustic Imaging for Monitoring Treatments against CT26 Tumors with Photoactivatable Liposomes

Cancers (Basel). 2021 Dec 31;14(1):197. doi: 10.3390/cancers14010197.

Authors

Ilya Turchin¹, Shazia Bano², Mikhail Kirillin¹, Anna Orlova¹, Valeriya Perekatova¹, Vladimir Plekhanov¹, Ekaterina Sergeeva¹, Daria Kurakina¹, Aleksandr Khilov¹, Alexey Kurnikov¹, Pavel Subochev¹, Marina Shirmanova³, Anastasiya Komarova³, Diana Yuzhakova³, Alena Gavrina³, Srivalleesha Mallidi^{2

4}, Tayyaba Hasan^{2

5}

Affiliations

¹ Institute of Applied Physics RAS, 46 Ulyanov St., 603950 Nizhny Novgorod, Russia.
² Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
³ Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, 10/1 Minin and Pozharsky Sq., 603005 Nizhny Novgorod, Russia.
⁴ Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA.
⁵ Division of Health Sciences and Technology, Harvard University and Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Abstract

The newly developed multimodal imaging system combining raster-scan optoacoustic (OA) microscopy and fluorescence (FL) wide-field imaging was used for characterizing the tumor vascular structure with 38/50 μm axial/transverse resolution and assessment of photosensitizer fluorescence kinetics during treatment with novel theranostic agents. A multifunctional photoactivatable multi-inhibitor liposomal (PMILs) nano platform was engineered here, containing a clinically approved photosensitizer, Benzoporphyrin derivative (BPD) in the bilayer, and topoisomerase I inhibitor, Irinotecan (IRI) in its inner core, for a synergetic therapeutic impact. The optimized PMIL was anionic, with the hydrodynamic diameter of 131.6 ± 2.1 nm and polydispersity index (PDI) of 0.05 ± 0.01, and the zeta potential between -14.9 ± 1.04 to -16.9 ± 0.92 mV. In the in vivo studies on BALB/c mice with CT26 tumors were performed to evaluate PMILs' therapeutic efficacy. PMILs demonstrated the best inhibitory effect of 97% on tumor growth compared to the treatment with BPD-PC containing liposomes (PALs), 81%, or IRI containing liposomes (L-[IRI]) alone, 50%. This confirms the release of IRI within the tumor cells upon PMILs triggering by NIR light, which is additionally illustrated by FL monitoring demonstrating enhancement of drug accumulation in tumor initiated by PDT in 24 h after the treatment. OA monitoring revealed the largest alterations of the tumor vascular structure in the PMILs treated mice as compared to BPD-PC or IRI treated mice. The results were further corroborated with histological data that also showed a 5-fold higher percentage of hemorrhages in PMIL treated mice compared to the control groups. Overall, these results suggest that multifunctional PMILs simultaneously delivering PDT and chemotherapy agents along with OA and FL multi-modal imaging offers an efficient and personalized image-guided platform to improve cancer treatment outcomes.

Keywords: fluorescence imaging; multi-inhibitor liposomes; nanoconstructs; optoacoustic imaging; photodynamic therapy; tumor vasculature.

Abstract

Grants and funding