Enzymatic dysregulation in tumor and intracellular microenvironments has made this property
a tremendously promising responsive element for efficient diagnostics, carrier targeting, and drug
release. When combined with nanotechnology, enzyme-responsive drug delivery systems (DDSs) have
achieved substantial advancements. In the first part of this tutorial review, changes in tumor and intracellular
microenvironmental factors, particularly the enzymatic index, are described. Subsequently, the
peptide sequences of various enzyme-triggered nanomaterials are summarized for their uses in various
drug delivery applications. Then, some other enzyme responsive nanostructures are discussed. Finally,
the future opportunities and challenges are discussed. In brief, this review can provide inspiration and
impetus for exploiting more promising internal enzyme stimuli-responsive nanoDDSs for targeted tumor
diagnosis and treatment.
Keywords: Tumor microenvironment, Enzyme-responsive, Peptide, Sequence, Targeted drug delivery, DDSs.
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