The
desire for all-organic-composed nanoparticles (NPs) of considerable
biocompatibility to simultaneously diagnose and treat cancer is undeniably
interminable. Heretofore, metal-based agents dominate the landscape
of available magnetic resonance imaging (MRI) contrast agents and
photothermal therapeutic agents, but with associated metal-specific
downsides. Here, an all-organic metal-free nanoprobe, whose appreciable
biocompatibility is synergistically contributed by its tetra-organo-components,
is developed as a viable alternative to metal-based probes for MRI-guided
tumor-targeted photothermal therapy (PTT). This rationally entails
a glycol chitosan (GC)-linked polypyrrole (PP) nanoscaffold that provides
abundant primary and secondary amino groups for amidation with the
carboxyl groups in a nitroxide radical (TEMPO) and folic acid (FA),
to obtain GC-PP@TEMPO-FA NPs. Advantageously, the appreciably benign
GC-PP@TEMPO-FA features high nitroxide loading (r
1 = 1.58 mM–1 s–1)
and in vivo nitroxide-reduction resistance, prolonged
nitroxide-systemic circulation times, appreciable water dispersibility,
potential photodynamic therapeutic and electron paramagnetic resonance
imaging capabilities, considerable biocompatibility, and ultimately
achieves a 17 h commensurate MRI contrast enhancement. Moreover, its
GC component conveys a plethora of PP to tumor sites, where FA-mediated
tumor targeting enables substantial NP accumulation with consequential
near-complete tumor regression within 16 days in an MRI-guided PTT.
The present work therefore promotes the engineering of organic-based
metal-free biocompatible NPs in synergism, in furtherance of tumor-targeted
image-guided therapy.