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

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.

Quantitative Characterization of Age-Related Changes in Peripheral Vessels of a Human Palm Using Raster-Scan Optoacoustic Angiography

“…In this paper, age-related changes in the vascular bed of the skin of healthy volunteers are assessed in vivo for the first time using the OA angiographic technique. As a criterion for analyzing age-related changes in the skin, various parameters of the vascular network of the skin were calculated using a recently developed [25] and successfully applied in [26] algorithm for processing the three-dimensional OA images based on graph representation of the vascular net. The proposed algorithm was used to calculate the parameters characterizing the average density of the vessels, the length of the vessels, and the branching of the vessels on the basis of a graph constructed from a skeletonized image.…”

Overview of Nanoparticle-Based Approaches for the Combination of Photodynamic Therapy (PDT) and Chemotherapy at the Preclinical Stage

“…In a similar approach, Turchin’s group proposed a liposomal photoactivatable multifunctional nanoplatform (PMIL) carrying a lipid-anchored derivative of BPD in the bilayer and IRI in an inner aqueous core [ 112 ]. In vivo studies on BALB/c mice injected with colon carcinoma CT26 cells demonstrated higher therapeutic efficacy (97% inhibition of tumor growth) following treatment with PMIL compared to BPD containing liposomes (81% inhibition) or IRI containing liposomes (50%).…”

Spotlight on Photoactivatable Liposomes beyond Drug Delivery: An Enabler of Multitargeting of Molecular Pathways

“…34 To maximize the therapeutic potential of PDT-based combination therapies several nanoformulations with PSs and chemotherapeutics have been reported. 34,59,91,160,161 Liang et al reported a nanoliposomal formulation combining Verteporfin and irinotecan where Verteporfin conjugated anti-EGFR antibodies (Photoimmunoconjugates; PIC) were further conjugated to irinotecan loaded liposomes generating the formulation PIC-Nanoliposomes (PIC-NL) (Figure 12A). 133 The efficacy of the construct was found to be EGFR specific and showed 20% more cytotoxicity as compared to the combination of PIC + Nal − IRI.…”