Provided herein are polypeptides that are selectively cleaved by cathepsin E. Also provided are methods of detecting cathepsin E. The methods comprise contacting cathepsin E with the polypeptides provided herein and detecting fluorescence. Further provided are methods of diagnosing cancer or pre-cancerous conditions in a subject. Also provided herein is a multilayered nanoparticle or a composition comprising the multilayer nanoparticle, wherein the multilayered nanoparticle comprises a negatively charged nanoparticle core or capsule coated with alternating positive and negative layers. Optionally, the positive layer comprises a positively charged protease degradable polypeptide. Optionally, the negative layer comprises a negatively charged therapeutic agent or a therapeutic agent and a means for providing the agent with a negative charge. For example, optionally, the therapeutic agent is linked to a negatively charged polymer. Further provided are methods of treating or preventing a disease characterized by expression of a protease in a subject using the nanoparticle.
