Abstract: In some aspects, the disclosure relates to compositions and method for detection, classification, and treatment of cancer. In some embodiments, the disclosure relates to protease imaging sensors comprising a scaffold linked to an enzyme-specific substrate that includes a first detectable marker capable of being released from the prostate protease sensor when exposed to an enzyme present in cancer and a tumor imaging agent comprising a second detectable marker that is linked to the scaffold. In some embodiments, the disclosure relates to methods of monitor progression of a tumor in a subject based upon detection of detectable markers in a sample obtained from a subject who has been administered a protease imaging sensor, upon detection of a tumor imaging agent, or any combination thereof.

Abstract: Spherical nucleic acids (SNAs), consisting of densely packed, highly oriented polynucleotide strands attached to the surface of nanoparticles, are able to overcome the typical challenges of nucleic acid delivery. The present disclosure demonstrates that G-rich SNAs exhibit several-fold higher uptake into cells relative to SNAs rich in other nucleotides. This disclosure provides an effective strategy to maximize the intracellular delivery of SNAs, which is applicable to other nanoparticle systems, thus establishing an important design consideration for nanoparticle-based intracellular delivery of therapeutics.

Abstract: Aspects of the present disclosure relate to methods and compositions useful for in vivo and/or in vitro profiling of environmental triggers (e.g., enzyme activity, pH or temperature). In some embodiments, the disclosure provides methods of in vivo enzymatic processing of exogenous molecules followed by detection of modified nucleic acid barcodes as representative of the presence of active enzymes (e.g., proteases) associated with a disease, for example, cancer. In some embodiments, the disclosure provides compositions and methods for production of in vivo sensors comprising modified nucleic acid barcodes.

Abstract: In some aspects, the disclosure relates to compositions and method for detection, classification, and treatment of cancer. In some embodiments, the disclosure relates to protease imaging sensors comprising a scaffold linked to an enzyme-specific substrate that includes a first detectable marker capable of being released from the prostate protease sensor when exposed to an enzyme present in cancer and a tumor imaging agent comprising a second detectable marker that is linked to the scaffold. In some embodiments, the disclosure relates to methods of monitor progression of a tumor in a subject based upon detection of detectable markers in a sample obtained from a subject who has been administered a protease imaging sensor, upon detection of a tumor imaging agent, or any combination thereof.

Abstract: Spherical nucleic acids (SNAs), consisting of densely packed, highly oriented polynucleotide strands attached to the surface of nanoparticles, are able to overcome the typical challenges of nucleic acid delivery. The present disclosure demonstrates that G-rich SNAs exhibit several-fold higher uptake into cells relative to SNAs rich in other nucleotides. This disclosure provides an effective strategy to maximize the intracellular delivery of SNAs, which is applicable to other nanoparticle systems, thus establishing an important design consideration for nanoparticle-based intracellular delivery of therapeutics.

Abstract: Provided herein are silica shell particles modified on their surface with biomolecules, methods of making these particles, and methods of using these particles, e.g., in transfection methods, methods of inhibiting gene expression, and methods of delivering a therapeutic.