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Review
. 2016 Oct 28:240:387-393.
doi: 10.1016/j.jconrel.2016.01.045. Epub 2016 Jan 28.

Biocomputing nanoplatforms as therapeutics and diagnostics

A C Evans  1 , N N Thadani  1 , J Suh  2
Affiliations
Review

Biocomputing nanoplatforms as therapeutics and diagnostics

A C Evans et al. J Control Release. .

Abstract

Biocomputing nanoplatforms are designed to detect and integrate single or multiple inputs under defined algorithms, such as Boolean logic gates, and generate functionally useful outputs, such as delivery of therapeutics or release of optically detectable signals. Using sensing modules composed of small molecules, polymers, nucleic acids, or proteins/peptides, nanoplatforms have been programmed to detect and process extrinsic stimuli, such as magnetic fields or light, or intrinsic stimuli, such as nucleic acids, enzymes, or pH. Stimulus detection can be transduced by the nanomaterial via three different mechanisms: system assembly, system disassembly, or system transformation. The increasingly sophisticated suite of biocomputing nanoplatforms may be invaluable for a multitude of applications, including medical diagnostics, biomedical imaging, environmental monitoring, and delivery of therapeutics to target cell populations.

Keywords: Boolean logic; Drug delivery; Gene therapy; Imaging agents; Logic gates; Nanoparticle; Review; Stimulus responsive; Targeted delivery.

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Figures

Figure 1
Figure 1
Biocomputing nanoplatforms accept inputs that are either intrinsic or extrinsic to biological systems, compute the inputs using defined functions, and produce outputs that manipulate the biological environment (therapeutics) or act as an externally detectable readout (diagnostics).
Figure 2
Figure 2
Methods of nanoplatform information processing fall into three broad categories: system assembly, system disassembly, and system transformation.
Figure 3
Figure 3
Nanoparticles functionalized with MMP-cleavable peptides can be used to detect MMP activity under defined logic gates. When the peptides are digested by the required combination of MMPs (yellow and green pacmans), binding sites are exposed, allowing the particles to aggregate and trigger an optical change. Figure used with permission [18].
Figure 4
Figure 4
A self-assembling nanoparticle undergoes AND-gate mediated disassembly and drug release during intracellular trafficking. First, acidic pH in the endosome induces nanoparticle disassembly, then the reducing environment of the cytoplasm breaks the disulfide bond linking the cancer drug doxorubicin (DOX) to polyethylene glycol (PEG). Figure used with permission [24].
Figure 5
Figure 5
Virus nanoparticles designed to be activated by two different MMPs for controlled gene delivery. Tunable virus nanoparticles are generated from the combination of two capsid proteins with different masking motifs (red or blue in schematic), each sensitive to a different MMP (red or blue pacmans). The mixed ‘mosaic capsid’ (middle row) demonstrates an AND-gate response to stimulation with the two different MMPs. The ‘analog response’ column displays heatmaps of the relative transduction index (rTI - the percent of fluorescence positive cells multiplied by the mean fluorescence intensity, normalized to control) of the given capsids in response to various concentration combinations of MMP inputs. Figure adapted and used with permission [36].
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