Indocyanine Green Liposomes for Diagnosis and Therapeutic Monitoring of Cerebral Malaria.
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ABSTRACT:
SUBMITTER: Portnoy E
PROVIDER: S-EPMC4729766 | biostudies-literature | 2016
REPOSITORIES: biostudies-literature
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Project description:Indocyanine green (ICG) is a clinically-approved near infrared (NIR) dye used for optical imaging. The dye is only slightly soluble in water and is prone to aggregation in saline solutions, so that alternative formulations can improve photophysical performance. Numerous nanoscale formulations of ICG have been described in the literature, but we sought to develop an approach that does not require additional purification steps. Pre-formed liposomes incorporating 45 mol% of the cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) rapidly bind ICG, resulting in enhanced NIR optical properties. ICG binding is dependent on the amount of DOTAP incorporated in the liposomes. A dye-to-lipid mass ratio of [0.5?:?25] is sufficient for full complexation, without additional purification steps following mixing. NIR absorption, fluorescence intensity, and photoacoustic signals are increased for the liposome-bound dye. Not only is the optical character enhanced by simple mixing of ICG with liposomes, but retention in 4T1 mammary tumors is observed following intratumor injection, as assessed by fluorescence and photoacoustic imaging. Subsequent photothermal therapy with 808 nm laser irradiation is effective and results in tumor ablation without regrowth for at least 30 days. Thus, ICG optical properties and photothermal ablation outcomes can be improved by mixing the dye with pre-formed DOTAP liposomes in conditions that result in full dye-binding to the liposomes.
| S-EPMC6650340 | biostudies-literature
Project description:C57BL/6 mice have more cerebral arterial branches and collaterals than BALB/c mice. We measured and compared blood flow dynamics of the middle cerebral artery (MCA) in these two strains, using noninvasive optical imaging with indocyanine green (ICG). Relative maximum fluorescence intensity (Imax) and the time needed for ICG to reach Imax in the MCA of C57BL/c were lower than that in BALB/c mice. Moreover, the mean transit time was significantly lower in C57BL/6 than in BALB/c mice. These data suggest that the higher number of arterial branches and collaterals in C57BL/6 mice yields a lower blood flow per cerebral artery.
| S-EPMC4640258 | biostudies-literature
Project description:Liposomes possess the potential to enhance drug solubility, prolong the duration of circulation, and augment drug accumulation at the tumor site through passive and active targeting strategies. However, there is a lack of studies examining the in vivo tumor penetration capabilities of liposomes of varying sizes, which hampers the development of drug delivery systems utilizing liposomal nanocarriers. Here, we present an indocyanine green (ICG)-loaded liposomes-assisted photoacoustic computed tomography (PACT) for directly evaluating the tumor penetration ability of liposomal nanocarriers in vivo. Through the utilization of microfluidic mixing combined with extrusion techniques, we successfully prepare liposomes encapsulating ICG in both large (192.6 ± 8.0 nm) and small (61.9 ± 0.6 nm) sizes. Subsequently, we designed a dual-wavelength PACT system to directly monitor the in vivo tumor penetration of large- and small-size ICG-encapsulated liposomes. In vivo PACT experiments indicate that ICG-loaded liposomes of smaller size exhibit enhanced penetration capability within tumor tissues. Our work presents a valuable approach to directly assess the penetration ability of liposomal nanocarriers in vivo, thereby facilitating the advancement of drug delivery systems with enhanced tumor penetration and therapeutic efficacy.
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Project description:BackgroundCerebral hyperperfusion syndrome (HPS) is a potentially life-threatening complication following carotid artery stenting (CAS) and carotid endoarterectomy (CEA). Early prediction and treatment of patients at risk for HPS are required in patients undergoing CAS because HPS occurs significantly earlier after CAS than CEA. Near-infrared spectroscopy (NIRS) is often used for monitoring, and indocyanine green (ICG) kinetics by NIRS (ICG-NIRS) can detect reductions in cerebral perfusion in patients with acute stroke. However, whether ICG-NIRS can predict postoperative hyperperfusion phenomenon (HP) after carotid revascularization is unclear.ObjectiveHere, we evaluated whether the blood flow index (BFI) ratio calculated from a time-intensity curve from ICG-NIRS monitoring can predict HPS after CAS.MethodsThe BFI ratio was prospectively monitored using ICG-NIRS in 135 patients undergoing CAS. Preoperative cerebrovascular reactivity (CVR) and the postoperative asymmetry index (AI) were also assessed with single-photon emission computed tomography before and after CAS, and the correlation was evaluated. In addition, patients were divided into two groups, a non-HP group (n = 113) and an HP group (n = 22), and we evaluated the correlation with hemodynamic impairment in the ipsilateral hemisphere and clinical results.ResultsTwenty-two cases (16%) showed HP, and four (3%) showed HPS after CAS. The BFI ratio calculated from ICG-NIRS showed a significant linear correlation with preoperative CVR and postoperative AI (r = -0.568, 0.538, P < 0.001, <0.001, respectively). The degree of stenosis, the rate of no cross flow, preoperative CVR, and the incidence of HPS were significantly different between the groups.ConclusionsMeasurement of ICG kinetics by NIRS is useful for detection of HPS in patients who underwent CAS.
| S-EPMC5507521 | biostudies-literature
Project description:In preclinical studies of ischemic brain disorders, it is crucial to measure cerebral blood flow (CBF); however, this requires radiological techniques with heavy instrumentation or invasive procedures. Here, we propose a noninvasive and easy-to-use optical imaging technique for measuring CBF in experimental small animals. Mice were injected with indocyanine green (ICG) via tail-vein catheterization. Time-series near-infrared fluorescence signals excited by 760 nm light-emitting diodes were imaged overhead by a charge-coupled device coupled with an 830 nm bandpass-filter. We calculated four CBF parameters including arrival time, rising time and mean transit time of a bolus and blood flow index based on time and intensity information of ICG fluorescence dynamics. CBF maps were generated using the parameters to estimate the status of CBF, and they dominantly represented intracerebral blood flows in mice even in the presence of an intact skull and scalp. We demonstrated that this noninvasive optical imaging technique successfully detected reduced local CBF during middle cerebral artery occlusion. We further showed that the proposed method is sufficiently sensitive to detect the differences between CBF status in mice anesthetized with either isoflurane or ketamine-xylazine, and monitor the dynamic changes in CBF after reperfusion during transient middle cerebral artery occlusion. The near-infrared optical imaging of ICG fluorescence combined with a time-series analysis of the molecular dynamics can be a useful noninvasive tool for preclinical studies of brain ischemia.
| S-EPMC3485229 | biostudies-literature
Project description:Multidrug resistance (MDR) of cancer cells remains a major obstacle to favorable outcomes of treatment with many drugs, including doxorubicin. Most of the clinical trials failed to demonstrate the benefit of the drug efflux transporter P-glycoprotein (P-gp) inhibitors to circumvent P-gp-mediated drug resistance in vivo. The present study explored the therapeutic potential of combined treatment with liposomal doxorubicin, P-gp inhibitor quinine, and the photodynamic therapy (PDT) using indocyanine green (ICG) in the adenocarcinoma drug-resistant tumor model. Liposomes were actively co-remotely loaded with doxorubicin and quinine, and ICG was passively adsorbed. The liposomes were characterized by differential scanning calorimetry (DSC) and cryogenic transmission microscopy (Cryo-TEM). We found that quinine impaired the crystalline structure of doxorubicin. In vitro, treatment with single agents themselves was insufficient to inhibit the growth of HT-29 MDR1 cells. However, pegylated liposomal doxorubicin and quinine (PLDQ) significantly diminished HT-29 MDR1 cell survival. Furthermore, survival inhibition intensified by the addition of ICG to the PLDQ (ICG + PLDQ). In vivo, ICG + PLDQ significantly decreased tumor growth when combined with tumor irradiation with NIR light (** p < 0.01). ICG + PLDQ + irradiation was superior to single treatments or combinational treatments without irradiation. These findings suggest that ICG + PLDQ can overcome P-gp-mediated MDR in cancer cells.
| S-EPMC8708987 | biostudies-literature
Project description:BackgroundEfficient cancer therapy is sought not only for primary tumor treatment but also for the prevention of metastatic cancer growth. Immunotherapy has been shown to prevent cancer metastasis by inducing antigen-specific immune responses. Indocyanine green (ICG) has a peak spectral absorption at about 800 nm, which makes it a photothermal reagent for direct treatment of solid tumors by photothermal therapy (PTT). Since PTT alone cannot fully induce antigen-specific immune response for prevention of cancer metastasis, the combination of PTT and immunotherapy has been developed as a new strategy of cancer treatment.MethodsThermal responsive liposomes (TRL) were synthesized by incorporating ICG into the lipid bilayer and encapsulating the water-soluble immune stimulatory molecule polyinosinic:polycytidylic acid (poly I:C) in the hydrophilic core. The poly I:C- and ICG-containing TRLs (piTRLs) were analyzed according to size, and their photothermal effect was evaluated following laser irradiation at 808 nm. Moreover, the temperature-dependent release of poly I:C was also measured. For cancer therapy, CT-26 (carcinoma) and B16 (melanoma) cells were subcutaneously inoculated to build the 1st transplanted tumor in BALB/c and C57BL/6 mice, respectively. These mice received a 2nd transplantation with the same cancer cells by intravenous inoculation, for evaluation of the anti-metastatic effects of the liposomes after PTT.ResultsNear-infrared (NIR) laser irradiation increased the temperature of piTRLs and effectively released poly I:C from the liposomes. The increased temperature induced a photothermal effect, which promoted cancer cell apoptosis and dissolution of the 1st transplanted tumor. Moreover, the released poly I:C from the piTRL induced activation of dendritic cells (DCs) in tumor draining lymph node (tdLN). Cancer cell apoptosis and DC-activation-mediated cancer antigen-specific immune responses further prevented growth of lung metastatic cancer developed following intravenous transplantation of cancer cells.ConclusionThese results demonstrated the potential usage of a piTRL with laser irradiation for immuno-photothermal therapy against various types of cancer and their metastases.
| S-EPMC6694491 | biostudies-literature
Project description:Cerebral malaria (CM) is a life-threatening neurological complication caused by Plasmodium falciparum. About 627,000 patients died of malaria in 2020. Currently, artemisinin and its derivatives are the front-line drugs used for the treatment of cerebral malaria. However, they cannot target the brain, which decreases their effectiveness. Therefore, increasing their ability to target the brain by the nano-delivery system with brain-targeted materials is of great significance for enhancing the effects of antimalarials and reducing CM mortality. This study used glucose transporter 1 (GLUT1) on the blood-brain barrier as a target for a synthesized cholesterol-undecanoic acid-glucose conjugate. The molecular dynamics simulation found that the structural fragment of glucose in the conjugate faced the outside the phospholipid bilayers, which was conducive to the recognition of brain-targeted liposomes by GLUT1. The fluorescence intensity of the brain-targeted liposomes (na-ATS/TMP@lipoBX) in the mouse brain was significantly higher than that of the non-targeted liposomes (na-ATS/TMP@lipo) in vivo (P < 0.001) after intranasal administration. The infection and recurrence rate of the mice receiving na-ATS/TMP@lipoBX treatment were significantly decreased, which had more advantages than those of other administration groups. The analysis of pharmacokinetic data showed that na-ATS/TMP@lipoBX could enter the brain in both systemic circulation and nasal-brain pathway to treat malaria. Taken together, these results in this study provide a new approach to the treatment of cerebral malaria.
| S-EPMC9258070 | biostudies-literature
Project description:There have been few anatomical structure segmentation studies using deep learning. Numbers of training and ground truth images applied were small and the accuracies of which were low or inconsistent. For a surgical video anatomy analysis, various obstacles, including a variable fast-changing view, large deformations, occlusions, low illumination, and inadequate focus occur. In addition, it is difficult and costly to obtain a large and accurate dataset on operational video anatomical structures, including arteries. In this study, we investigated cerebral artery segmentation using an automatic ground-truth generation method. Indocyanine green (ICG) fluorescence intraoperative cerebral videoangiography was used to create a ground-truth dataset mainly for cerebral arteries and partly for cerebral blood vessels, including veins. Four different neural network models were trained using the dataset and compared. Before augmentation, 35,975 training images and 11,266 validation images were used. After augmentation, 260,499 training and 90,129 validation images were used. A Dice score of 79% for cerebral artery segmentation was achieved using the DeepLabv3+ model trained using an automatically generated dataset. Strict validation in different patient groups was conducted. Arteries were also discerned from the veins using the ICG videoangiography phase. We achieved fair accuracy, which demonstrated the appropriateness of the methodology. This study proved the feasibility of operating field view of the cerebral artery segmentation using deep learning, and the effectiveness of the automatic blood vessel ground truth generation method using ICG fluorescence videoangiography. Using this method, computer vision can discern blood vessels and arteries from veins in a neurosurgical microscope field of view. Thus, this technique is essential for neurosurgical field vessel anatomy-based navigation. In addition, surgical assistance, safety, and autonomous surgery neurorobotics that can detect or manipulate cerebral vessels would require computer vision to identify blood vessels and arteries.
| S-EPMC8790180 | biostudies-literature
Project description:ObjectiveDelineation of the intersegmental plane during pulmonary segmentectomy by systemic injection of indocyanine green (ICG) has been rapidly emerging. We evaluated the feasibility of the use of ICG in a large-scale cohort according to the type of segmentectomy and the presence of obstructive lung disorder and compared the demarcation status with air injection.MethodsWe collected the data of 209 patients who underwent segmentectomy using ICG at National Cancer Center Hospital, Tokyo, Japan. Data of the operation including the demarcation status of the intersegmental plane were analyzed retrospectively.ResultsThe median operation duration and blood loss were 105 minutes (interquartile range, 94-118 minutes) and 12 mL (interquartile range, 5-24 mL), respectively. Good demarcation of the intersegmental plane by ICG was observed in 184 (88.0%) cases, with no correlation to the type of resected segments or the presence of obstructive lung disorder. Postoperative complications of Clavien-Dindo classification grade 3 or more were observed in 5 cases (2.4%), and no ICG-related adverse event was noted. High-frequency jet ventilation was also used in 160 cases (76.6%) to delineate the intersegmental inflation-deflation plane. The air injected by high-frequency jet ventilation tended to spread further beyond the intersegmental plane that was depicted by ICG.ConclusionsThe use of ICG might demarcate the intersegmental plane more restricted to the target segment compared with air injection. Delineation of the intersegmental plane by ICG is feasible regardless of the type of segmentectomy or the presence of obstructive lung disorder, and it can be commonly applicable in pulmonary segmentectomy.
| S-EPMC8300924 | biostudies-literature