AND-gated protease-activated nanosensors for programmable detection of anti-tumour immunity.

The forward design of biosensors that implement Boolean logic to improve detection precision primarily relies on programming genetic components to control transcriptional responses. However, cell- and gene-free nanomaterials programmed with logical functions may present lower barriers for clinical translation. Here we report the design of activity-based nanosensors that implement AND-gate logic without genetic parts via bi-labile cyclic peptides.

Urinary detection of early responses to checkpoint blockade and of resistance to it via protease-cleaved antibody-conjugated sensors.

Immune checkpoint blockade (ICB) therapy does not benefit the majority of treated patients, and those who respond to the therapy can become resistant to it. Here we report the design and performance of systemically administered protease activity sensors conjugated to anti-programmed cell death protein 1 (αPD1) antibodies for the monitoring of antitumour responses to ICB therapy. The sensors consist of a library of mass-barcoded protease substrates that, when cleaved by tumour proteases and immune proteases, are released into urine, where they can be detected by mass spectrometry.

Interfacing Biomaterials with Synthetic T Cell Immunity.

The clinical success of cancer immunotherapy is providing exciting opportunities for the development of new methods to detect and treat cancer more effectively. A new generation of biomaterials is being developed to interface with molecular and cellular features of immunity and ultimately shape or control anti-tumor responses. Recent advances that are supporting the advancement of engineered T cells are focused here.

Non-invasive early detection of acute transplant rejection via nanosensors of granzyme B activity.

The early detection of the onset of transplant rejection is critical for the long-term survival of patients. The diagnostic gold standard for detecting transplant rejection involves a core biopsy, which is invasive, has limited predictive power and carries a morbidity risk. Here, we show that nanoparticles conjugated with a peptide substrate specific for the serine protease granzyme B, which is produced by recipient T cells during the onset of acute cellular rejection, can serve as a non-invasive biomarker of early rejection.

Nanosensors to Detect Protease Activity In Vivo for Noninvasive Diagnostics.

Proteases are multi-functional enzymes that specialize in the hydrolysis of peptide-bonds and control broad biological processes including homeostasis and allostasis. Moreover, dysregulated protease activity drives pathogenesis and is a functional biomarker of diseases such as cancer; therefore, the ability to detect protease activity in vivo may provide clinically relevant information for biomedical diagnostics. The goal of this protocol is to create nanosensors that probe for protease activity in vivo by producing a quantifiable signal in urine.