Polymer–iron oxide composite nanoparticles for EPR-independent drug delivery

Abstract

Nanoparticle (NP)-based approaches to cancer drug delivery are challenged by the heterogeneity of the enhanced permeability and retention (EPR) effect in tumors and the premature attrition of payload from drug carriers during circulation. Here we show that such challenges can be overcome by a magnetophoretic approach to accelerate NP delivery to tumors. Payload-bearing poly(lactic-co-glycolic acid) NPs were converted into polymer–iron-oxide nanocomposites (PINCs) by attaching colloidal Fe3O4 onto the surface, via a simple surface modification method using dopamine polymerization. PINCs formed stable dispersions in serum-supplemented medium and responded quickly to magnetic field gradients above 1 kG/cm. Under the field gradients, PINCs were rapidly transported across physical barriers and into cells and captured under flow conditions similar to those encountered in postcapillary venules, increasing the local concentration by nearly three orders of magnitude. In vivo magnetophoretic delivery enabled PINCs to accumulate in poorly vascularized subcutaneous SKOV3 xenografts that did not support the EPR effect. In vivo magnetic resonance imaging, ex vivo fluorescence imaging, and tissue histology all confirmed that the uptake of PINCs was higher in tumors exposed to magnetic field gradients, relative to negative controls.

Organic nanoparticle systems for spatiotemporal control of multimodal chemotherapy

“…Finding a fine balance between the stability and timely drug release is an ongoing challenge, which is frequently overlooked in nanomedicine research due to inappropriate characterization methods [139]. The latter approach, often involving external stimuli such as ultrasound or magnetic forces, is found effective in counteracting premature drug release during circulation, at least in preclinical studies [140]. However, the need for the use of external stimuli and corresponding materials may complicate the product design and application, which may hamper clinical translation of the technology.…”

Intracellular in situ labeling of TiO2 nanoparticles for fluorescence microscopy detection

“…Click chemistry itself is simple, highly selective, efficient, and reproducible. Finally, similar staining and detection techniques could be applicable to other metal oxide nanoparticles like iron oxide, which also has a high affinity for dopamine [44, 45]. …”

Lipid nanoparticle-based co-delivery of epirubicin and BCL-2 siRNA for enhanced intracellular drug release and reversing multidrug resistance

“…The particle average size is 120 nm (Figure 2(B)). The appropriate size (<200 nm) can preferentially accumulated in the tumor region via EPR effect [28][29][30]. The zeta potential is 41 mV (Figure 2(B)), which can easily uptake by cells with high positive charge.…”