Real-time monitoring of magnetic drug targeting using fibered confocal fluorescence microscopy

Abstract

Magnetic drug targeting has been proposed as means of concentrating therapeutic agents at a target site and the success of this approach has been demonstrated in a number of studies. However, the behavior of magnetic carriers in blood vessels and tumor microcirculation still remains unclear. In this work, we utilized polymeric magnetic nanocapsules (m-NCs) for magnetic targeting in tumors and dynamically visualized them within blood vessels and tumor tissues before, during and after magnetic field exposure using fibered confocal fluorescence microscopy (FCFM). Our results suggested that the distribution of m-NCs within tumor vasculature changed dramatically, but in a reversible way, upon application and removal of a magnetic field. The m-NCs were concentrated and stayed as clusters near a blood vessel wall when tumors were exposed to a magnetic field but without rupturing the blood vessel. The obtained FCFM images provided in vivo in situ microvascular observations of m-NCs upon magnetic targeting with high spatial resolution but minimally invasive surgical procedures. This proof-of-concept descriptive study in mice is envisaged to track and quantify nanoparticles in vivo in a non-invasive manner at microscopic resolution.

AKT2 siRNA delivery with amphiphilic-based polymeric micelles show efficacy against cancer stem cells

“…Our results showed that there is no aggregation with serum components up to 12 h of incubation, suggesting that this PM may be adequate for intravenous administration in vivo , since as for other micellar systems, a circulation half-life under 12 h is expected (Rijcken et al., 2007 ). Moreover, our results with in vivo FCFM imaging show that PM can be observed in circulation up to 4 h postadministration and that nanosystems are able to leave the vascular bed and extravasate into the tumor parenchyma, probably due to the presence of leaky vasculature of the tumors, as previously demonstrated by FCFM technique in animal models (Bai et al., 2016 ). This process would ensure the enhanced permeability and retention (EPR) effect (Matsumura & Maeda, 1986 ; Maeda et al., 2000 ) and would help to increase the efficacy of the siRNA.…”

Controllably Switched Drug Release from Successively Dual‐Targeted Nanoreservoirs

“…Thus, they are easily excreted from the mice body after postinjection of several days through the urine and faeces due to the biodegradation of MSN, and the biodegradation byproducts from these MMSNs are nontoxic to the biological tissues . However, this inhibition rate by magnetic targeting is influenced by many factors, such as: the magnetic saturation of the nanocarriers, the strength of the externally applied magnetic field, the tumor type, and the tumor vascularity . So, we expect to design a more stronger magnetic nanocarrier under more stronger magnetic field to enhance the anticancer ability.…”

Shedding light on fibered confocal fluorescence microscopy: Applications in biomedical imaging and therapies

“…EVs have the potential to be used as natural nanoparticles carriers for delivery of therapeutic agents for disease treatment . The imaging and distribution of EVs in vivo are important for the development and optimization of EV‐based therapy, and FCFM has been shown to be suitable for in vivo imaging of polymeric magnetic nanoparticles bearing therapeutic agents within mouse blood vessels and tumors . The resolution and sensitivity of FCFM with the Cellvizio system also enables the accurate ex‐vivo detection and visualization of fluorescently labeled EVs (Figure ); therefore can therefore be used to gain knowledge of EV uptake mechanisms in vivo.…”