Photoacoustic imaging of tumor targeting with riboflavin-functionalized theranostic nanocarriers

Abstract

Photoacoustic imaging is an emerging method in the molecular imaging field, providing high spatiotemporal resolution and sufficient imaging depths for many clinical applications. Therefore, the aim of this study was to use photoacoustic imaging as a tool to evaluate a riboflavin (RF)-based targeted nanoplatform. RF is internalized by the cells through a specific pathway, and its derivatives were recently shown as promising tumor-targeting vectors for the drug delivery systems. Here, the RF amphiphile synthesized from a PEGylated phospholipid was successfully inserted into a long-circulating liposome formulation labeled with the clinically approved photoacoustic contrast agent – indocyanine green (ICG). The obtained liposomes had a diameter of 124 nm (polydispersity index =0.17) and had a negative zeta potential of −26 mV. Studies in biological phantoms indicated a stable and concentration-dependent photoacoustic signal (Vevo ® LAZR) of the ICG-containing RF-functionalized liposomes. In A431 cells, a high uptake of RF-functionalized liposomes was found and could be blocked competitively. First, studies in mice revealed ~3 times higher photoacoustic signal in subcutaneous A431 tumor xenografts ( P <0.05) after injection of RF-functionalized liposomes compared to control particles. In this context, the application of a spectral unmixing protocol confirmed the initial quantitative data and improved the localization of liposomes in the tumor. In conclusion, the synthesized RF amphiphile leads to efficient liposomal tumor targeting and can be favorably detected by photoacoustic imaging with a perspective of theranostic applications.

AS1411 aptamer-modified theranostic liposomes co-encapsulating manganese oxide nano-contrast agent and paclitaxel for MRI and therapy of cancer

“…39 First, 300 mL liposome-PEG-MnO nanocomplex (4 mM Mn) was injected via tail-vein into the BALB/c mice. Then, 10 mL peripheral blood was collected from the tail vein at different time points (5,15,30,45,60,120,180,240,360, 720 and 1440 minutes). The obtained blood was mixed with heparin sodium (90 mL) in separate tubes and digested with HNO 3 for Mn concentration determination by ICP-MS.…”

“…[4][5][6][7] Except for the use as a drug delivery carrier, theranostic liposomes have been concerned more and more in recent years due to the demand of the simultaneous diagnosis and therapy. Such theranostic liposomes are commonly obtained by the co-encapsulation of drugs and imaging molecules, such as uorescent quantum dots, 8,9 magnetic resonance imaging contrast agents (MRI CAs), [10][11][12][13] CT imaging contrast agents, 14 photoacoustic imaging CAs, 15 and ultrasound imaging CAs. 16 Among them, MRI-based theranostic liposomes own special advantages, because MRI is a widely used non-invasive medical imaging technique in clinical diagnosis.…”

Folate-receptor-targeted laser-activable poly(lactide-<em>co</em>-glycolic acid) nanoparticles loaded with paclitaxel/indocyanine green for photoacoustic/ultrasound imaging and chemo/photothermal therapy

“…In the in vitro gel experiment of PA imaging, spectra of the NPs within the NIR region were analyzed by the PA-imaging system. The PA signal peaked at 800 nm ( Figure S2), due to the excellent absorption of ICG, 41 which was selected as the excitation NIR wavelength in the following experiments. As shown in Figure 2D and E, the PA signal strengthened linearly with increased concentration of FA-PEG-PLGA-Ptx@ICG-Pfh NPs from 2 to 10 mg/mL.…”

Photoacoustic imaging to localize indeterminate pulmonary nodules: A preclinical study

“…ICG-encapsulated nanoparticles have been explored as an option to overcome these limitations. However, one report stated that that PA signal from ICG liposome was clearly resolved to a depth of 10 mm using chicken breast muscle [29], which is not appropriate for IPN localization. Our phantom study demonstrated that the PA signal increased logarithmically without a…”