Diketopyrrolopyrrole Derivatives Grafting Hyaluronic Acid for Targeted Photodynamic Therapy

Photodynamic therapy (PDT) can effectively avoid the damages on the normal tissues and organs compared to the traditional cancer treatment methods because of its non-invasive property for the body and high selectivity to tumor site upon light irradiation. Rational design of photosensitizers (PSs) with specific targeting towards tumors and on-site activation is strongly desirable for precise cancer photodynamic therapy. Herein, a novel hydrophilic tumor-targeting photosensitizer (DTDPP-HA) is synthesized by covalently coupling 2,5-bis-(6-bromo-hexyl)-3,6-di-thiophen-2-yl-2,5-dihydro-pyrrolo[3,4-c]pyrrole-1,4-dione (DTDPP) with hyaluronic acid (HA), which presents high singlet oxygen generation and specific targeting to the CD44 receptor overexpressed cancer cells, as well as low dark toxicity and high phototoxicity. More important, both vitro and vivo experiments reveal that DTDPP-HA can effectively suppress tumor growth. Therefore, the DTDPP-HA would be a potential and promising theranostic agent for PDT.