As fossil fuels are increasingly linked to environmental damage, the development of renewable, affordable biological alternative fuels is vital. Shewanella oneidensis is often suggested as a potential component of bioelectrochemical cells because of its ability to act as an electron donor to metal surfaces. These microbes remain challenging to implement, though, due to inconsistency in biofilm formation on electrodes and therefore current generation. We have applied DNA hybridization-based cell adhesion to immobilize S. oneidensis on electrodes. High levels of current are reproducibly generated from these cell layers following only 30 min of immobilization without the need for the formation of a biofilm. Upon incorporation of DNA mismatches in the microbe immobilization sequence, significant attenuation in current production is observed, suggesting that at least part of the electron transfer to the electrode is DNA-mediated. This method of microbe assembly is rapid, reproducible, and facile for the production of anodes for biofuel cells.

The favorable properties of cyanines (e.g., nearinfrared (NIR) absorbance and emission) have made this class of dyes popular for a wide variety of biomedical applications. However, many cyanines are prone to rapid photobleaching when irradiated with light. In this study, we have exploited this undesirable trait to develop NIR-nanogels for NIR light-mediated cargo delivery. NIR-nanogels feature a photolabile cyanine crosslinker (Cy780-Acryl) that can cleave via dioxetane chemistry when irradiated. This photochemical process results in the formation of two carbonyl fragments and concomitant NIR-nanogel degradation to facilitate cargo release. In contrast to studies where cyanines are utilized as photocages, our approach does not require direct chemical attachment to the cargo, thus expanding our ability to deliver molecules that cannot be covalently modified. We showcase this feature by encapsulating a palette of small-molecule chemotherapeutics that feature a structurally diverse chemical architecture. To demonstrate site-selective release in vivo, we generated a murine model of breast cancer. Relative to nonlight irradiated and drugfree controls, treatment with NIR-nanogels loaded with paclitaxel (a potent cytotoxic agent) and NIR light resulted in significant attenuation of tumor growth. Moreover, we show via histological staining of the vital organs that minimal off-target effects are observed.

SWIR dyes offer many advantages over their more common NIR congeners; however, the available options are limited. New SWIR imaging agents can be accessed by remodeling existing NIR molecules (i.e., hemicyanines (HDs)). In this study, we synthesized SWIR-HD, a modified HD featuring dimethylsilicon and benzo[cd]indolium groups that are designed to red-shift the absorbance and emission to 988 and 1126 nm, respectively. SWIR-HD was employed to visualize the liver and tumors via multimodal SWIR imaging.

The attachment of glucose to drugs and imaging agents enables cancer cell targeting via interactions with GLUT1 overexpressed on the cell surface. While an added benefit of this modification is the solubilizing effect of carbohydrates, in the context of imaging agents, aqueous solubility does not guarantee decreased π-stacking or aggregation. The resulting broadening of the absorbance spectrum is a detriment to photoacoustic (PA) imaging since the signal intensity, accuracy, and image quality all rely on reliable spectral unmixing. To address this major limitation and further enhance the tumor-targeting ability of imaging agents, we have taken a biomimetic approach to design a multivalent glucose moiety (mvGlu). We showcase the utility of this new group by developing aza-BODIPY-based contrast agents boasting a significant PA signal enhancement greater than 11-fold after spectral unmixing. Moreover, when applied to targeting cancer cells, effective staining could be achieved with ultra-low dye concentrations (50 nM) and compared to a non-targeted analogue, the signal intensity was >1000-fold higher. Lastly, we employed the mvGlu technology to develop a logic-gated acoustogenic probe to detect intratumoral copper (i.e., Cu(I)), which is an emerging cancer biomarker, in a murine model of breast cancer. This exciting application was not possible using other acoustogenic probes previously developed for copper sensing.

The earliest activity-based photoacoustic (PA) probes were developed as diagnostic agents for cancer. Since this seminal work over a decade ago that specifically targeted matrix metalloproteinase-2, PA instrumentation, dye platforms, and probe designs have advanced considerably, allowing for the detection of an impressive list of cancer types. However, beyond imaging for oncology purposes, the ability to selectively visualize a given disease biomarker, which can range from aberrant enzymatic activity to the overproduction of reactive small molecules, is also being exploited to study a myriad of noncancerous disease states. In this review, we have assembled a collection of recent papers to highlight the design principles that enable activity-based sensing via PA imaging with respect to biomarker identification and strategies to trigger probe activation under specific conditions.