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ICG-Loaded PEG-Modified Black Phosphorus Nanosheets for Fluorescence Imaging-Guided Breast Cancer Therapy.

ABSTRACT: Indocyanine green (ICG) has been used in various surgical navigation systems and plays an important role in intraoperative imaging diagnosis. However, the poor photostability and unsatisfactory tumor-targeting ability have limited its broad application prospects. In the decades, the construction of a nanodrug delivery system for tumor-targeting diagnosis and therapy has become a research hotspot. Black phosphorus nanosheets (BPNS), as a new kind of biodegradable nanomaterials, have the advantages of high loading capacity, good biocompatibility, tumor targeting, and photothermal effect over other two-dimensional (2D) reported nanomaterials. Herein, ICG-loaded poly(ethylene glycol) (PEG)-modified BPNS (ICG@BPNS-PEG) nanocomposites are constructed to improve the tumor-targeting capacity and guide photothermal therapy through real-time fluorescence imaging. In this study, ICG@BPNS-PEG nanocomposites with a suitable size (240 ± 28 nm) have been successfully constructed. The photostability of ICG@BPNS-PEG nanocomposites surpassed that of free ICG after four on-off cycles of near laser irradiation (NIR). Moreover, ICG@BPNS-PEG nanocomposites have enhanced photothermal conversion ability. The cellular uptake result through flow cytometry showed that ICG@BPNS-PEG nanocomposites could be swallowed easily owing to the suitable size and passive cellular uptake. In addition, the cytotoxicity evaluation of MCF-7, 4T1 breast cancer cells, and healthy RPE cells through the MTT assay demonstrated that ICG@BPNS-PEG nanocomposites have lower cytotoxicity and good cellular compatibility without irradiation. However, the cytotoxicity and live/dead staining proved that ICG@BPNS-PEG nanocomposites have satisfactory photothermal therapeutic effects when irradiated. In the 4T1-bearing mice model, the fluorescence imaging after intravenous injection of nanocomposites showed that ICG@BPNS-PEG nanocomposites have superior passive tumor targeting accumulation through the enhanced permeability and retention (EPR) effect compared with that of free ICG. Also, changes in tumor volume showed a remarkable tumor growth inhibition effect compared with other groups. Moreover, the results of hematoxylin-eosin (H&E) staining of major organs in 4T1-bearing mice also demonstrated that the nanocomposites have good biocompatibility. Therefore, the constructed ICG@BPNS-PEG nanocomposites have substantial potential in breast cancer therapy.

SUBMITTER: Pan W

PROVIDER: S-EPMC8717538 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundSmall bowel malperfusion (SBM) can cause high morbidity and severe surgical consequences. However, there is no standardized objective measuring tool for the quantification of SBM. Indocyanine green (ICG) imaging can be used for visualization, but lacks standardization and objectivity. Hyperspectral imaging (HSI) as a newly emerging technology in medicine might present advantages over conventional ICG fluorescence or in combination with it.MethodsHSI baseline data from physiological small bowel, avascular small bowel and small bowel after intravenous application of ICG was recorded in a total number of 54 in-vivo pig models. Visualizations of avascular small bowel after mesotomy were compared between HSI only (1), ICG-augmented HSI (IA-HSI) (2), clinical evaluation through the eyes of the surgeon (3) and conventional ICG imaging (4). The primary research focus was the localization of resection borders as suggested by each of the four methods. Distances between these borders were measured and histological samples were obtained from the regions in between in order to quantify necrotic changes 6 h after mesotomy for every region.ResultsStO2 images (1) were capable of visualizing areas of physiological perfusion and areas of clearly impaired perfusion. However, exact borders where physiological perfusion started to decrease could not be clearly identified. Instead, IA-HSI (2) suggested a sharp-resection line where StO2 values started to decrease. Clinical evaluation (3) suggested a resection line 23 mm (±7 mm) and conventional ICG imaging (4) even suggested a resection line 53 mm (±13 mm) closer towards the malperfused region. Histopathological evaluation of the region that was sufficiently perfused only according to conventional ICG (R3) already revealed a significant increase in pre-necrotic changes in 27% (±9%) of surface area. Therefore, conventional ICG seems less sensitive than IA-HSI with regards to detection of insufficient tissue perfusion.ConclusionsIn this experimental animal study, IA-HSI (2) was superior for the visualization of segmental SBM compared to conventional HSI imaging (1), clinical evaluation (3) or conventional ICG imaging (4) regarding histopathological safety. ICG application caused visual artifacts in the StO2 values of the HSI camera as values significantly increase. This is caused by optical properties of systemic ICG and does not resemble a true increase in oxygenation levels. However, this empirical finding can be used to visualize segmental SBM utilizing ICG as contrast agent in an approach for IA-HSI. Clinical applicability and relevance will have to be explored in clinical trials.Level of evidenceNot applicable. Translational animal science. Original article.

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ICG-Loaded PEG-Modified Black Phosphorus Nanosheets for Fluorescence Imaging-Guided Breast Cancer Therapy.

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