Cancer is one of the deadliest diseases of our time throughout the world. The traditional cancer treatments, including surgery, radiation therapy and chemotherapy, result in serious side effects caused by the loss of normal organ function. In contrast, photodynamic therapy (PDT) is more controllable and has the potential to selectively destroy malignant cells while sparing the normal tissues and thus is recognized as a treatment strategy which is both minimally invasive and minimally toxic.

Among many types of photosensitizers for PDT, phthalocyanine (Pc) is one of main classes of photosensitizers for PDT with optimal photophysical and photochemical properties. Its longer maximal absorption wavelength (670 nm) can give a deeper tissue penetration (about twice) compared to the wavelength at 630 nm, which is typically used for porfimer sodium (Photofrin), an effective photosensitizer currently in clinical use. However, phthalocyanines tend to have low tumor-targeting efficacy, which limits the use of phthalocyanine in clinical applications.

The research groups headed by Prof. HUANG Mingdong and Prof. CHEN Xueyuan at Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, have developed a simple and unique strategy to prepare a hydrophilic tumor-targeting photosensitizer ATF-ZnPc by covalently coupling zinc phthalocyanine (ZnPc) to the amino-terminal fragment (ATF) of urokinase-type plasminogen activator (uPA), a fragment responsible for uPA receptor (uPAR, a biomarker over-expressed in cancer cells), through the carboxyl groups of ATF. They have demonstrated for the first time that a higher specificity can be achieved when Pcs are targeted towards tumor specific receptors, which may also facilitate specific drug delivery.

Furthermore, they have also showed the in vivo optical imaging applications of such tumor-targeting PDT agent in H22 tumor-bearing mice. Results of this study have been published as a full article in ACTA BIOMATERIALIA (2014, DOI: 10.1016/j.actbio.2014.06.026).

Conjugation of ATF with zinc phthalocyanine (ZnPc) renders ZnPc soluble in water and generates a high degree of specificity to uPAR-abundant tumor cells. (Image by Prof. HUANG Mingdong's group)