Harnessing nanotechnology to expand the toolbox of chemical biology.

Although nanotechnology often addresses biomedical needs, nanoscale tools can also facilitate broad biological discovery. Nanoscale delivery, imaging, biosensing, and bioreactor technologies may address unmet questions at the interface between chemistry and biology. Currently, many chemical biologists do not include nanomaterials in their toolbox, and few investigators develop nanomaterials in the context of chemical tools to answer biological questions.

Glutathione-S-transferase Fusion Protein Nanosensor.

Fusion protein tags are widely used to capture and track proteins in research and industrial bioreactor processes. Quantifying fusion-tagged proteins normally requires several purification steps coupled with classical protein assays. Here, we developed a broadly applicable nanosensor platform that quantifies glutathione-S-transferase (GST) fusion proteins in real-time.

Synthetic molecular recognition nanosensor paint for microalbuminuria.

Microalbuminuria is an important clinical marker of several cardiovascular, metabolic, and other diseases such as diabetes, hypertension, atherosclerosis, and cancer. The accurate detection of microalbuminuria relies on albumin quantification in the urine, usually via an immunoturbidity assay; however, like many antibody-based assessments, this method may not be robust enough to function in global health applications, point-of-care assays, or wearable devices. Here, we develop an antibody-free approach using synthetic molecular recognition by constructing a polymer to mimic fatty acid binding to the albumin, informed by the albumin crystal structure.

An Nanosensor Measures Compartmental Doxorubicin Exposure.

Preclinical measurements of drug exposure to specific organs and tissues is normally performed by destructive methods. Tissue-specific measurements are important, especially for drugs with intractable dose-limiting toxicities, such as doxorubicin-mediated cardiotoxicity. We developed a method to rapidly quantify doxorubicin exposure to tissues within living organisms using an implantable optical nanosensor that can be interrogated noninvasively following surgical implantation.

HIV Detection via a Carbon Nanotube RNA Sensor.

Viral illnesses remain a significant concern in global health. Rapid and quantitative early detection of viral oligonucleotides without the need for purification, amplification, or labeling would be valuable in guiding successful treatment strategies. Single-walled carbon nanotube-based sensors recently demonstrated optical detection of small, free oligonucleotides in biofluids and in vivo, although proteins diminished sensitivity.

Noninvasive ovarian cancer biomarker detection via an optical nanosensor implant.

Patients with high-grade serous ovarian carcinoma (HGSC) exhibit poor 5-year survival rates, which may be significantly improved by early-stage detection. The U.S.

Control of Carbon Nanotube Solvatochromic Response to Chemotherapeutic Agents.

Alkylating agents such as cisplatin play an essential role in chemotherapy regimens, but initial and acquired resistance in many cancer types often dampen therapeutic response. The poor understanding of the mechanisms of resistance highlight the need for quantitative measurements of alkylating agent distribution at both the tissue and subcellular levels. Sensors for use in live animals and cells would allow for more effective study of drug action and resistance.

A Carbon Nanotube Optical Reporter Maps Endolysosomal Lipid Flux.

Lipid accumulation within the lumen of endolysosomal vesicles is observed in various pathologies including atherosclerosis, liver disease, neurological disorders, lysosomal storage disorders, and cancer. Current methods cannot measure lipid flux specifically within the lysosomal lumen of live cells. We developed an optical reporter, composed of a photoluminescent carbon nanotube of a single chirality, that responds to lipid accumulation via modulation of the nanotube's optical band gap.

A Carbon Nanotube Reporter of miRNA Hybridization Events In Vivo.

MicroRNAs and other small oligonucleotides in biofluids are promising disease biomarkers, yet conventional assays require complex processing steps that are unsuitable for point-of-care testing or for implantable or wearable sensors. Single-walled carbon nanotubes are an ideal material for implantable sensors, owing to their emission in the near-infrared spectral region, photostability and exquisite sensitivity. Here, we report an engineered carbon-nanotube-based sensor capable of real-time optical quantification of hybridization events of microRNA and other oligonucleotides.

Polymer cloaking modulates the carbon nanotube protein corona and delivery into cancer cells.

Carbon nanotube-based molecular probes, imaging agents, and biosensors in cells and in vivo continue to garner interest as investigational tools and clinical devices due to their unique photophysical properties. Surface chemistry modulation of nanotubes plays a critical role in determining stability and interaction with biological systems both in vitro and in vivo. Among the many parameters that influence the biological fate of nanomaterials, surface charge is particularly influential due to direct electrostatic interactions with components of the cell membrane as well as proteins in the serum, which coat the nanoparticle surface in a protein corona and alter nanoparticle-cell interactions.

ADCC develops over time during persistent infection with live-attenuated SIV and is associated with complete protection against SIV(mac)251 challenge.

Live-attenuated strains of simian immunodeficiency virus (SIV) routinely confer apparent sterilizing immunity against pathogenic SIV challenge in rhesus macaques. Understanding the mechanisms of protection by live-attenuated SIV may provide important insights into the immune responses needed for protection against HIV-1. Here we investigated the development of antibodies that are functional against neutralization-resistant SIV challenge strains, and tested the hypothesis that these antibodies are associated with protection.

A panel of IgG1 b12 variants with selectively diminished or enhanced affinity for Fcγ receptors to define the role of effector functions in protection against HIV.

Passive transfer of neutralizing antibodies is effective in protecting rhesus macaques against simian/human immunodeficiency virus (SHIV) challenge. In addition to neutralization, effector functions of the crystallizable fragment (Fc) of antibodies are involved in antibody-mediated protection against a number of viruses. We recently showed that interaction between the Fc fragment of the broadly neutralizing antibody IgG1 b12 and cellular Fcγ receptors (FcγRs) plays an important role in protection against SHIV infection in rhesus macaques.