Folate Receptor-Targeted and Cathepsin B‑Activatable
Nanoprobe for <i>In Situ</i> Therapeutic Monitoring of Photosensitive Cell Death
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Abstract
The
integration of diagnostic and therapeutic functions in a single
system holds great promise to enhance the theranostic efficacy and
prevent the under- or overtreatment. Herein, a folate receptor-targeted
and cathepsin B-activatable nanoprobe is designed for background-free
cancer imaging and selective therapy. The nanoprobe is prepared by
noncovalently assembling phospholipid-poly(ethylene oxide) modified
folate and photosensitizer-labeled peptide on the surface of graphene
oxide. After selective uptake of the nanoprobe into lysosome of cancer
cells via folate receptor-mediated endocytosis, the peptide can be
cleaved to release the photosensitizer in the presence of cancer-associated
cathepsin B, which leads to 18-fold fluorescence enhancement for cancer
discrimination and specific detection of intracellular cathepsin B.
Under irradiation, the released photosensitizer induces the formation
of cytotoxic singlet oxygen for triggering photosensitive lysosomal
cell death. After lysosomal destruction, the lighted photosensitizer
diffuses from lysosome into cytoplasm, which provides a visible method
for <i>in situ</i> monitoring of therapeutic efficacy. The
nanoprobe exhibits negligible dark toxicity and high phototoxicity
with the cell mortality rate of 0.06% and 72.1%, respectively, and
the latter is specific to folate receptor-positive cancer cells. Therefore,
this work provides a simple but powerful protocol with great potential
in precise cancer imaging, therapy, and therapeutic monitoring