Hoechst 33258–conjugated hyaluronated fullerene for efficient photodynamic tumor therapy and necrotic tumor targeting

In this study, we synthesized a Hoechst 33258–conjugated hyaluronated fullerene consisting of Hoechst 33258 (as a target moiety to detect necrotic tumor cells), hyaluronic acid (as a target polymer to bind the CD44 receptor overexpressed on the surface of tumor cells), and fullerene (as a photosensitizing agent). This conjugate self-assembled to form nanoparticles consisting of a hydrophilic block (Hoechst 33258 and hyaluronic acid) and a lipophilic block (fullerene). We utilized these nanoparticles to improve the antitumor efficacy via photodynamic tumor therapy. The HCT-116 cells that were damaged after the first photodynamic tumor therapy (using hyaluronated fullerene nanoparticles) were again targeted using Hoechst 33258–conjugated hyaluronated fullerene nanoparticles (detecting necrotic tissues). The experimental results revealed that the second photodynamic tumor therapy using Hoechst 33258–conjugated hyaluronated fullerene nanoparticles caused significant increases in the in vitro phototoxicity and the in vivo tumor inhibition, thereby suggesting their pharmaceutical potential for designing effective multiple photodynamic tumor therapy treatments.