Nanotechnology: emerging tools for biology and medicine

Abstract

Historically, biomedical research has been based on two paradigms. First, measurements of biological behaviors have been based on bulk assays that average over large populations. Second, these behaviors have then been crudely perturbed by systemic administration of therapeutic treatments. Nanotechnology has the potential to transform these paradigms by enabling exquisite structures comparable in size with biomolecules as well as unprecedented chemical and physical functionality at small length scales. Here, we review nanotechnology-based approaches for precisely measuring and perturbing living systems. Remarkably, nanotechnology can be used to characterize single molecules or cells at extraordinarily high throughput and deliver therapeutic payloads to specific locations as well as exhibit dynamic biomimetic behavior. These advances enable multimodal interfaces that may yield unexpected insights into systems biology as well as new therapeutic strategies for personalized medicine.

Keywords: Nanoparticle; biomarker; microfluidics; microneedle; single cell; targeted delivery.

Figure 1.

Key themes underlying nanotechnology in biology and medicine, including new capabilities to measure or perturb cells in vitro as well as diagnose or treat patients. An exciting prospect is the future integration of these different capabilities for biomimetic behaviors such as adaption, self-organization, and amplification.

Figure 2.

(A) DNA “Lego-like” bricks for three-dimensional cuboid structures. (B) DNA sheets assembled into curved and anisotropic geometries. (C) Nanoparticles of different materials, shapes, and sizes fabricated using PRINT. (D) Multicomponent barcoded particles fabricated using flow lithography. From Pregibon et al. (2007) and Ke et al. (2012). Reprinted with permission from AAAS. Reprinted from Shih and Lin (2010), with permission from Elsevier. Reprinted from Wang et al. (2011a); © 2011 Wiley-VCH Verlag GmbH & Co., KGaA, Weinheim.

Figure 3.

(A) Sequencing DNA with hybrid biological–artificial nanopores. (B) Measuring cell-secreted ROS using carbon nanotubes. (C) Electrophysiology in three-dimensonal (3D) scaffolds using nanowire arrays. (D) Mechanical deformation of 3D scaffolds using traction force microscopy. (E) Growth of adherent cells measured using microresonators. (F) Growth of cells in solution measured using suspended mass resonators. Reprinted by permission from Macmillan Publishers Ltd. from Hall et al. (2010), Jin et al. (2010), Legant et al. (2010), Son et al. (2012), and Tian et al. (2012). Reproduced with permission from Park et al. (2010).

Figure 4.

(A) One-picoliter droplets can be dispensed, moved, merged, mixed, and split in an open geometry using electric fields. (B) Droplet libraries can be challenged against a reactant and then sorted at ultrahigh throughput in channels. From Wheeler (2008). Reprinted with permission from AAAS. Reproduced from Guo et al. (2012) with permission of The Royal Society of Chemistry.

Figure 5.

(A) Integrated barcode chip for proteomic biomarkers from blood. (B) Protein typing of circulating microvesicles using miniaturized NMR. (C) Antigen-dependent and -independent enrichment of rare tumor cells using magnetic nanoparticles. (D) Multiplexed synthetic biomarkers are amplified by enzymatic cleavage near tumors followed by renal concentration for noninvasive monitoring of disease progression. Reprinted by permission from Macmillan Publishers Ltd. from Fan et al. (2008) and Shao et al. (2012).

Figure 6.

(A) Arrays of silicon nanowires can deliver siRNA into the interior of dendritic cells. Dissolving polymer microneedles (B) can deliver influenza vaccine to defined locations beneath the skin (C). Reprinted by permission from Macmillan Publishers Ltd. from Sullivan et al. (2010). Reprinted with permission from Shalek et al. (2012). © 2012 American Chemical Society.

Figure 7.

(A) Nanoparticle consisting of a degradable polymeric core loaded with drugs protected by a “stealth” polymer brush shell with targeting ligands. (B) Amplified targeting of nanoparticles by locally induced coagulation. From Hrkach et al. (2012). Reprinted with permission from AAAS. Reprinted by permission from Macmillan Publishers Ltd. from von Maltzahn et al. (2011).