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A novel liver-specific fluorescent anti-cancer drug delivery system using indocyanine green.

ABSTRACT: Indocyanine green (ICG) accumulates only in hepatocytes and their malignant counterpart, hepatocellular carcinoma (HCC). We have developed ICG-conjugated anti-cancer drugs and noted their significant accumulation in HCC cells both in vitro and in vivo. ICG-conjugated gemcitabine was less toxic to normal cells and it had superior anti-tumor action compared to gemcitabine alone in a subcutaneous tumor xenograft. ICG conjugation can provide a novel fluorescent drug delivery system for treatment of liver cancer and this system can be used to both diagnose and treat HCC.

SUBMITTER: Inagaki Y

PROVIDER: S-EPMC6395603 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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A novel liver-specific fluorescent anti-cancer drug delivery system using indocyanine green.

Inagaki Yoshinori Y Kokudo Takashi T Kamiya Mako M Uno Shin-Nosuke SN Sato Masumitsu M Kaneko Junichi J Kokudo Norihiro N Urano Yasuteru Y Hasegawa Kiyoshi K

Scientific reports 20190228 1

Indocyanine green (ICG) accumulates only in hepatocytes and their malignant counterpart, hepatocellular carcinoma (HCC). We have developed ICG-conjugated anti-cancer drugs and noted their significant accumulation in HCC cells both in vitro and in vivo. ICG-conjugated gemcitabine was less toxic to normal cells and it had superior anti-tumor action compared to gemcitabine alone in a subcutaneous tumor xenograft. ICG conjugation can provide a novel fluorescent drug delivery system for treatment of ...[more]

PMID: 30816163

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Project description:ObjectivesEvaluation of intestinal perfusion remains subjective and depends on the surgeon´s individual experience. Intraoperative quality assessment of tissue perfusion with indocyanine green (ICG) fluorescence using a near-infrared camera system has been described in different ways and for different indications. The aim of the present study was to evaluate fluorescent imaging (FI) in the quantitative assessment of intestinal perfusion in a gastric tube model in pigs and to compare the results to results obtained with florescent microspheres (FM), the gold standard for tissue perfusion.MethodsSeven pigs (56.0±3.0 kg), both males and females, underwent gastric tube formation after transection and ligation of the gastric arteries, except the right gastroepiploic artery, to avoid collateral blood flow. After baseline assessment (T0), hypotension (T1) was induced by propofol (Karampinis et al 2017) (< 60 mmHg). Then, propofol was paused to obtain normotension (T2, Mean arterial pressure (MAP) 60-90 mmHg). Finally, hypertension (T3, MAP>90 mmHg) was induced by norepinephrine. Measurements were performed in three regions of interest (ROIs) under standardized conditions: the fundus (D1), corpus (D2), and prepyloric area (D3). Hemodynamic parameters and transit-time flow measurement (TTFM) in the right gastroepiploic artery were continuously assessed. FI, FM and the partial pressure of tissue oxygen (TpO2) were quantified in each ROI.ResultsThe study protocol could successfully be performed during stable hemodynamics. Flow in the gastroepiploic artery measured by transit time flow measurement (TTFM) was related to hemodynamic changes between the measurements, indicating improved blood flow with increasing MAP. The distal part of the gastric tube (D1) showed significantly (p<0.05) impaired perfusion compared to the proximal parts D3 and D2 using FM. ICG-FI also showed the highest values in D3 and the lowest values in D1 at all hemodynamic levels (T1-T3; p<0,05).ConclusionVisual and quantitative assessment of gastric tube perfusion is feasible in an experimental setting using ICG-FI. This might be a promising tool for intraoperative assessment during visceral surgery in the future.

Dataset Information

A novel liver-specific fluorescent anti-cancer drug delivery system using indocyanine green.

Publications

A novel liver-specific fluorescent anti-cancer drug delivery system using indocyanine green.

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