In Vitro and in Vivo Visualization and Trapping of Fluorescent Magnetic Microcapsules in a Bloodstream

Abstract

Remote navigation and targeted delivery of biologically active compounds is one of the current challenges in the development of drug delivery systems. Modern methods of micro- and nanofabrication give us new opportunities to produce particles and capsules bearing cargo to deploy and possess magnetic properties to be externally navigated. In this work we explore multilayer composite magnetic microcapsules as targeted delivery systems in vitro and in vivo studies under natural conditions of living organism. Herein, we demonstrate magnetic addressing of fluorescent composite microcapsules with embedded magnetite nanoparticles in blood flow environment. First, the visualization and capture of the capsules at the defined blood flow by the magnetic field are shown in vitro in an artificial glass capillary employing a wide-field fluorescence microscope. Afterward, the capsules are visualized and successfully trapped in vivo into externally exposed rat mesentery microvessels. Histological analysis shows that capsules infiltrate small mesenteric vessels whereas large vessels preserve the blood microcirculation. The effect of the magnetic field on capsule preferential localization in bifurcation areas of vasculature, including capsule retention at the site once external magnet is switched off is discussed. The research outcome demonstrates that microcapsules can be effectively addressed in a blood flow, which makes them a promising delivery system with remote navigation by the magnetic field.

Detection of Rare Objects by Flow Cytometry: Imaging, Cell Sorting, and Deep Learning Approaches

“…The application of the external magnetic field is another reliable way of highly selective cell manipulation by the external force [155]. This is achievable since biological materials have a very low magnetic susceptibility, and thus, the cells labeled with magnetic particles or that having the intrinsic magnetic properties can be effectively isolated without the interference with the surrounding medium and objects [156].…”

Cell‐Based Drug Delivery and Use of Nano‐and Microcarriers for Cell Functionalization

“…The interactions of nano‐ and microcarriers with cells have been mainly studied with the use of FFC and confocal laser scanning microscopy . FFC is suitable for the quantitative analysis of the efficiency of dendritic cells to internalize magnetic capsules ( Figure ).…”

Real-time monitoring of tumor vascular disruption induced by radiofrequency assisted gadofullerene

“…Hepatoma 22 cells (H22) (5×10 6 tumor cells in 100 μL of saline) were injected subcutaneously into the mice in the right rear flank area. The experiments were conducted when the tumors reached a volume of 100 mm 3 5-7 days after the tumor inoculation. The tumors were irradiated in the 300 MHz RF generator for 1.5 h via an intravenous injection of GFNC solution (50 mg kg -1 ) for treatment and using saline as a control.…”

“…Compared with the normal vasculature, the tumor blood vessels usually have abnormal morphology [2], such as incomplete vessel walls, loose cell-cell connections between the tumor endothelial cells, and structurally abnormal basement membrane, etc. [3][4][5][6][7]. Moreover, the blood flow of tumor vasculature is often sluggish and some blood vessels are not continuously perfused [8,9], leading to the observed hyper-permeability and high interstitial fluid pressure in solid tumors [10][11][12][13].…”