Nanoparticle Beacons: Supersensitive Smart Materials with On/Off-Switchable Affinity to Biomedical Targets

Abstract

Smart materials that can switch between different states under the influence of chemical triggers are highly demanded in biomedicine, where specific responsiveness to biomarkers is imperative for precise diagnostics and therapy. Superior selectivity of drug delivery to malignant cells may be achieved with the nanoagents that stay “inert” until “activation” by the characteristic profile of microenvironment cues (e.g., tumor metabolites, angiogenesis factors, microRNA/DNA, etc.). However, despite a wide variety and functional complexity of smart material designs, their real-life applications are hindered by very limited sensitivity to inputs. Here, we present ultrasensitive smart nanoagents with input-dependent On/Off switchable affinity to a biomedical target based on a combination of gold nanoparticles with low-energy polymer structures. In the proposed method, a nanoparticle-based agent is surface coated with a custom designed flexible polymer chain, which has an input-switchable structure that regulates accessibility of the terminal receptor for target binding. Implementation of the concept with a DNA-model of such polymer has yielded nanoagents that have input-dependent cell-targeting capabilities and responsiveness to as little as 30 fM of DNA input in 15 min lateral flow assay. Thus, we show that surface phenomena can augment nanoagents with capability for switchable affinity without compromising the sensitivity to inputs. The proposed approach is promising for development of next-generation theranostic agents and ultrasensitive nanosensors for point-of-care diagnostics.

Theranostics Based on Magnetic Nanoparticles and Polymers: Intelligent Design for Efficient Diagnostics and Therapy

“…Each constituent of these multicomponent particles plays an important role in theranostic applications. Other examples of a combination of gold and magnetic NPs were reported by Cherkasov et al (2020), Wang et al (2018), and (Sun et al, 2016).…”

“…Functionalization of core-shell iron oxide NP-polymer constructs with FA allows for enhanced targeting and uptake in tumor cells FIGURE 2 | Schematic representation of the NP beacon action (Cherkasov et al, 2020). Reproduced with the permission of the copyright holder (American Chemical Society).…”

“…A NP beacon based on gold and ferrihydrite NPs coated with a flexible polymer (custom designed amino-group terminated oligonucleotides with terminal biotin) was fabricated by conjugation using streptavidin and DNA to form a highly sensitive input-switchable structure (Cherkasov et al, 2020 ). This structure controls accessibility of the terminal receptor for binding to the target ( Figure 2 ).…”

“… Schematic representation of the NP beacon action (Cherkasov et al, 2020 ). Reproduced with the permission of the copyright holder (American Chemical Society).…”

Spindle-like MRI-active europium-doped iron oxide nanoparticles with shape-induced cytotoxicity from simple and facile ferrihydrite crystallization procedure

“…One of the rapidly developing applications of nanostructured materials is the construction of nanoagents capable of detection and selective elimination of pathogens including bacterial infections and cancer cells. [1][2][3][4]56 Such agents are usually constructed using a nanoparticle as a base. This particle may have no function but bearing surface-modied layers of reagents for selective detection, imaging, and killing pathogen cells.…”