An activatable multimodal/multifunctional nanoprobe for direct imaging of intracellular drug delivery

Abstract

Multifunctional nanoparticles integrated with imaging modalities (such as magnetic resonance and optical) and therapeutic drugs are promising candidates for future cancer diagnostics and therapy. While targeted drug delivery and imaging of tumor cells have been the major focus in engineering nanoparticle probes, no extensive efforts have been made towards developing sensing probes that can confirm and monitor intra-cellular drug release events. Here, we present quantum dot (Qdot)-iron oxide (IO) based multimodal/multifunctional nanocomposite probe that is optically and magnetically imageable, targetable and capable of reporting on intra-cellular drug release events. Specifically, the probe consists of a superparamagnetic iron oxide nanoparticle core (IONP) decorated with satellite CdS:Mn/ZnS Qdots where the Qdots themselves are further functionalized with STAT3 inhibitor (an anti-cancer agent), vitamin folate (as targeting motif) and m-polyethylene glycol (m-PEG, a hydrophilic dispersing agent). The Qdot luminescence is quenched in this nanocomposite probe (“OFF” state) due to combined electron/energy transfer mediated quenching processes involving IONP, folate and STAT3 agents. Upon intracellular uptake, the probe is exposed to the cytosolic glutathione (GSH) containing environment resulting in restoration of the Qdot luminescence (“ON” state), which reports on uptake and drug release. Probe functionality was validated using fluorescence and MR measurements as well as in vitro studies using cancer cells that overexpress folate receptors.

Yttrium oxide nanoparticles prevent photoreceptor death in a light-damage model of retinal degeneration

“…Transmission electron microscopy (TEM) analysis was carried out as described [30, 31] using one drop of a 1 mM or 5 μM Y 2 O 3 NP (Sigma-Aldrich Inc.) dispersion which was prepared under 10W ultrasonication at room temperature.…”

Fluorescence-based ion-sensing with colloidal particles

“…for fluorescence resonance energy transfer, FRET) [12], ligands for colloidal stability or for targeting, or therapeutic compounds [13,14], and thus permits an exceptional tailoring in the design of these systems. In case magnetic nanoparticles are used as carriers the same system could act magnetically guided as drug delivery carrier, which simultaneously monitors the delivered drug [15]. Also polyelectrolyte capsules are a very universal system toward the integration of many different functional units into one particle [16], in addition to the actual ion-sensitive fluorophores [17].…”

Controlling and Monitoring Intracellular Delivery of Anticancer Polymer Nanomedicines

“…The increased QD fluorescence could be used to track STAT3 release from the nanocomposite and the iron oxide core allowed MRI analysis of the nanocomposite in the cell cytoplasm. [209] In addition to following drug release from polymer conjugates or polymer nanomedicines, a second important challenge is to monitor endosomal escape of polymer nanomedicines and/or their cargo. The use of CLSM and suitable labels allows to monitor either drug or carrier.…”