Nanoparticles for imaging, sensing, and therapeutic intervention

Abstract

Nanoparticles have the potential to contribute to new modalities in molecular imaging and sensing as well as in therapeutic interventions. In this Nano Focus article, we identify some of the current challenges and knowledge gaps that need to be confronted to accelerate the developments of various applications. Using specific examples, we journey from the characterization of these complex hybrid nanomaterials; continue with surface design and (bio)physicochemical properties, their fate in biological media and cells, and their potential for cancer treatment; and finally reflect on the role of animal models to predict their behavior in humans.

Figure 1

Schematic of (left) a noble metal nanoparticle (NP) with thiol and disulfide surface coatings and (right) a metal oxide NP with carboxylate and phosphonate coatings. R represents a functional group or recognition unit. The left cartoon implies metal–sulfur bonding; the right implies metal cation–anion bonding.

Figure 2

Schematic of randomly arranged molecular adsorbates on a nanoparticle (NP) surface (left), compared to adsorbates arranged in patches (right) on a NP surface.

Figure 3

Chemical structures of (a) poly(ethylene) glycol (PEG), (b) sulfobetaine, and (c) carboxybetaine.

Figure 4

Nanoparticle (NP) cycle. To generate NPs through bottom-up or top-down fabrication requires energy that the formed NPs tend to dissipate either by aggregation or by chemical transformation.

Figure 5

Schematic illustrating magnetically induced hyperthermia and drug release. (A) Magnetic nanoparticles (NPs) at a defined concentration, when exposed to an alternating magnetic field, can induce a temperature rise as a consequence of their magnetic vibrations. (B) Heat produced locally by the magnetic NP can be used to release drugs associated to the NP surface via thermosensitive linkers.⁻ In this case, drug release could occur even if the global temperature of the system does not change macroscopically; a local temperature increase is responsible for such release.^,,

Figure 6

Iteraction of different lipid-based nanoparticles (LNPs) with subsets of leukocytes can suppress or activate the immune response. The first line of defense by the innate immune arm includes different pattern recognition receptors such as membrane-bound toll-like receptors (TLRs), cytoplasmic NOD-like receptors (NLRs), and scavenger receptors on innate immune cells such as monocytes, macrophages, and dendritic cells. The second line of defense includes the adaptive immune arm with several important T helper subsets such as T_H1, T_H2, T_H17, T_regs, T_H9, and T_H22 cells. Each subset of leukocytes can interact differently with different types of nanoparticles made from different materials and with different sizes, geometries, and surface charges. Adapted with permission from ref (114). Copyright 2012 Elsevier B.V.

Figure 7

Schematic representation of different mechanisms by which nanocarriers can deliver drugs to tumors. Multifunctional lipid-based nanoparticles (LNPs) coencapsulated with chemotherapeutic drug (orange dots) and siRNA are shown as representative nanocarriers. Passive tissue targeting is achieved by extravasation of nanoparticles (NPs) through increased permeability of the tumor vasculature and ineffective lymphatic drainage (EPR effect). Active cellular targeting (inset) can be achieved by decorating the surface of NPs with multiple targeting moieties that promote cell-specific recognition and binding. The NPs can reach different tumor subpopulations concomitantly (i.e., tumor cells and tumor “nurse-like” macrophages) to ensure maximal therapeutic effect and release their contents in close proximity to the target cells, attach to the membrane of the cell, and act as an extracellular sustained-release drug depot or internalize into the cell, introducing their payload to cell cytoplasm.