Polyoxazoline multivalently conjugated with indocyanine green for sensitive in vivo photoacoustic imaging of tumors

Abstract

Photoacoustic imaging, which enables high-resolution imaging in deep tissues, has lately attracted considerable attention. For tumor imaging, photoacoustic probes have been proposed to enhance the photoacoustic effect to improve detection sensitivity. Here, we evaluated the feasibility of using a biocompatible hydrophilic polymer, polyoxazoline, conjugated with indocyanine green (ICG) as a tumor-targeted photoacoustic probe via enhanced permeability and retention effect. ICG molecules were multivalently conjugated to partially hydrolyzed polyoxazoline, thereby serving as highly sensitive photoacoustic probes. Interestingly, loading multiple ICG molecules to polyoxazoline significantly enhanced photoacoustic signal intensity under the same ICG concentration. In vivo biodistribution studies using tumor bearing mice demonstrated that 5% hydrolyzed polyoxazoline (50 kDa) conjugated with ICG (ICG/polyoxazoline = 7.8), P14-ICG7.8, showed relatively high tumor accumulation (9.4%ID/g), resulting in delivery of the highest dose of ICG among the probes tested. P14-ICG7.8 enabled clear visualization of the tumor regions by photoacoustic imaging 24 h after administration; the photoacoustic signal increased in proportion with the injected dose. In addition, the signal intensity in blood vessels in the photoacoustic images did not show much change, which was attributed to the high tumor-to-blood ratios of P14-ICG7.8. These results suggest that polyoxazoline-ICG would serve as a robust probe for sensitive photoacoustic tumor imaging.

Low-grade myofibroblastic sarcoma of the orbit

“…[ 31 ] The third one is photoacoustic imaging, which could detect highly sensitive and high-resolution photoacoustic signals in deep tissues. [ 32 ] Thus, we speculated that new molecular imaging techniques could be helpful for preoperative diagnosis, therapy, and prognosis estimate in LGMS. Unfortunately, due to the lack of the new molecular imaging system, this patient was not performed these specific examinations before surgery.…”

<p>Combined Therapeutic Effects of ¹³¹I-Labeled and 5Fu-Loaded Multifunctional Nanoparticles in Colorectal Cancer</p>

“…ICG, approved for clinical use by the US Food and Drug Administration, is highly biocompatible and has been widely used for tumor cell imaging. 32 In this study, we evaluated the cellular uptake of nanoparticles through encapsulating ICG using a confocal fluorescence microscope (Figure 2). The results showed that the fluorescence intensity of cells treated with Cet-PEG-PLA-ICG was significantly higher than that of cells treated with PEG-PLA-ICG.…”

Brachytherapy with Intratumoral Injections of Radiometal-Labeled Polymers That Thermoresponsively Self-Aggregate in Tumor Tissues

“…Thermoresponsive POZ derivatives including EtPOZ composed of 2-ethyl-2-oxazoline, IspPOZ composed of 2-isopropyl-2-oxazoline, Isp-PrPOZ composed of 2-isopropyl-2-oxazoline and 2-propyl-2-oxazoline, and PrPOZ composed of 2-propyl-2-oxazoline were synthesized according to previous reports (11,16). The reaction scheme is shown in Figure 2.…”

“…Poly (2-alkyl-2-oxazoline) (POZ), an isomeric polypeptide material that can be synthesized via living cationic ring-opening polymerization (8), is garnering attention as a biocompatible and hydrophilic biomaterial for drug delivery (9,10), in addition to the more traditional polyethylene glycol. Recently, we have demonstrated that chemically modified POZ accumulates in tumor tissue via an enhanced permeability and retention effect and is rapidly cleared from the blood after intravenous injection of the probe (11), indicating its usefulness for biomedical applications. Moreover, POZ has a lower critical solution temperature and can self-aggregate above a specific transition temperature (Tt) that is dependent on the oxazoline composition and molecular weight of its polymers (12,13), which can be controlled in a range of 10°C-90°C.…”