Combining magnetic nanoparticles with cell derived microvesicles for drug loading and targeting

Abstract

Inspired by microvesicle-mediated intercellular communication, we propose a hybrid vector for magnetic drug delivery. It consists of macrophage-derived microvesicles engineered to enclose different therapeutic agents together with iron oxide nanoparticles. Here, we investigated in vitro how magnetic nanoparticles may influence the vector effectiveness in terms of drug uptake and targeting. Human macrophages were loaded with iron oxide nanoparticles and different therapeutic agents: a chemotherapeutic agent (doxorubicin), tissue-plasminogen activator (t-PA) and two photosensitizers (disulfonated tetraphenyl chlorin-TPCS2a and 5,10,15,20-tetra(m-hydroxyphenyl)chlorin-mTHPC). The hybrid cell microvesicles were magnetically responsive, readily manipulated by magnetic forces and MRI-detectable. Using photosensitizer-loaded vesicles, we showed that the uptake of microvesicles by cancer cells could be kinetically modulated and spatially controlled under magnetic field and that cancer cell death was enhanced by the magnetic targeting. From the clinical editor: In this article, the authors devised a biogenic method using macrophages to produce microvesicles containing both iron oxide and chemotherapeutic agents. They showed that the microvesicles could be manipulated by magnetic force for targeting and subsequent delivery of the drug payload against cancer cells. This smart method could provide a novel way for future fight against cancer.

Tissue plasminogen activator-based nanothrombolysis for ischemic stroke

“…They found that co-incubation of iron oxide nanoparticles did not influence the uptake of tPA, and tPA localized at the cytoplasm after endocytosis. This novel hybrid cell microvesicles could be manipulated by magnetic force for targeting delivery of tPA to blood clots 47 . Lately, Tadayon et al developed an extracellular biosynthesis of nanoparticles (CuNP) for the simultaneously targeted delivery of tPA and streptokinase (SK) 48 .…”

Towards Therapeutic Delivery of Extracellular Vesicles: Strategies for In Vivo Tracking and Biodistribution Analysis

“…Moreover, in some EVs-producing cells, especially primary cells, it might be difficult to achieve a satisfactory level of transgene expression, using both viral and nonviral methods of transduction. To avoid genetic manipulation, Silva et al loaded the EVs-secreting cells with iron oxide particles to produce EVs-containing magnetic nanoparticles suitable for magnetic targeting [75]. Alternatively, a series of approaches aiming at modifying the EVs after secretion, without the need of manipulating the EVs-producing cells, have been recently pursued (Figure 2).…”

Fabrication and Cytotoxicity of Gemcitabine-Functionalized Magnetite Nanoparticles

“…Nowadays, the use of magnetic nanoparticles as drug transporters has been an area of significant interest [5]. Besides its biocompatibility, one reason for using magnetite Fe 3 O 4 nanoparticles in this type of delivery system, is given by the possibility of applying any of the previously mentioned targeting approaches: passive by EPR [6], and active by magnetic targeting [7,8,9,10] or specific functionalizing [11,12,13,14]. Fe 3 O 4 nanoparticles have been already used as carriers for GEM in some in vitro approaches aiming to improve the drug release time [15], and efficiency [16,17].…”