Enzyme-mediated intratumoral self-assembly of nanotheranostics for enhanced imaging and tumor therapy.

Abstract

Enzyme-mediated intratumoral self-assembled (EMISA) nanotheranostics represent a new class of smart agents for combined imaging and therapy of cancer. Cancer cells overexpress various enzymes that are essential for high metabolism, fast proliferation, and tissue invasion and metastasis. By conjugating small molecules that contain an enzyme-specific cleavage site to appropriate chemical linkers, it is possible to induce self-assembly of nanostructures in tumor cells having the target enzyme. This approach of injecting small theranostic molecules that eventually become larger nanotheranostics in situ avoids some of the major limitations that are encountered when injecting larger, pre-assembled nanotheranostics. The advantage of EMISA nanotheranostics include the avoidance of nonspecific uptake and rapid clearance by phagocytic cells, increased cellular accumulation, reduced drug efflux and prolonged cellular exposure time, all of which lead to an amplified imaging signal and therapeutic efficacy. We review here the different approaches that can be used for preparing EMISA-based organic, inorganic, or organic/inorganic hybrid nanotheranostics based on noncovalent interactions and/or covalent bonding. Imaging examples are shown for fluorescence imaging, nuclear imaging, photoacoustic imaging, Raman imaging, computed tomography imaging, bioluminescent imaging, and magnetic resonance imaging. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Biology-Inspired Nanomaterials > Peptide-Based Structures.