Photodynamic therapy (
PDT) is a novel treatment modality that is under intensive preclinical investigations for a variety of diseases, including
cancer. Despite extensive studies in this area, selective and effective photodynamic agents that can specifically accumulate in
tumors to reach a therapeutic concentration are limited. Although recent attempts have produced
photosensitizers (PSs) complexed with various nanomaterials, the tedious preparation steps and poor
tumor efficiency of
therapy hamper their utilization. Here, we developed a CD44-targeted nanophotodynamic agent by physically encapsulating a
photosensitizer, Ce6, into a
hyaluronic acid nanoparticle (HANP), which was hereby denoted HANP/Ce6. Its physical features and capability for
photodynamic therapy were characterized in vitro and in vivo. Systemic delivery of HANP/Ce6 resulted in its accumulation in a human
colon cancer xenograft model. The
tumor/muscle ratio reached 3.47 ± 0.46 at 4 h post injection, as confirmed by fluorescence imaging.
Tumor growth after HANP/Ce6 treatment with
laser irradiation (0.15 W/cm2, 630 nm) was significantly inhibited by 9.61 ± 1.09-fold compared to that in
tumor control groups, which showed no change in
tumor growth. No apparent systemic and local toxic effects on the mice were observed. HANP/Ce6-mediated
tumor growth inhibition was accessed and observed for the first time by 18F-fluoro-2-deoxy-d-glucose positron emission tomography as early as 1 day
after treatment and persisted for 14 days within our treatment time window. In sum, our results highlight the imaging properties and
therapeutic effects of the novel HANP/Ce6
theranostic nanoparticle for CD44-targeted
PDT cancer therapy that may be potentially utilized in the clinic. This HANP system may also be applied for the delivery of other hydrophobic PSs, particularly those that could not be chemically modified.