In vivo selective cancer-tracking gadolinium eradicator as new-generation photodynamic therapy agent

• Published in: Proceedings of the National Academy of Sciences - PNAS 2014-12, Vol.111 (51), p.E5492-E5497
• Main Authors: Zhang, Tao, Lan, Rongfeng, Chan, Chi-Fai, Law, Ga-Lai, Wong, Wai-Kwok, Wong, Ka-Leung
• Format: Article
• Language: English
• Subjects: adverse effects; animal models; Animals; blood vessels; Cancer therapies; Chemical elements; Cytotoxicity; Drug Delivery Systems; gadolinium; Gadolinium - therapeutic use; Humans; Lasers; medicine; Membranes; Mice; monitoring; neoplasms; Neoplasms - drug therapy; Oncology; Photochemotherapy; Photodynamic therapy; Physical Sciences; PNAS Plus; singlet oxygen; therapeutics; tissues; transportation
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1414499111

Significance Next-generation photodynamic therapy (NG-PDT) for the treatment of tumors preponderates over conventional practices in that it is a kind of effective precision medicine with minimal invasive procedures and side effects. Herein, a newly developed NG-PDT paradigm agent of gadolinium-porphyrin complex, Gd-N, is introduced, which can successfully trace and recognize tumor tissues via simple injection into the blood vessel of the mouse models, selectively accumulate within them, and superiorly exert the therapeutic effect via cytotoxic singlet oxygen generation (∼51% quantum yield) to eradicate the solid tumor by one-half within a short period of time only upon due two-photon excitation. Its characteristic two-photon–induced near-infrared emission is also always available for direct monitoring for transportation and effectiveness in vitro and in vivo. In this work, we demonstrate a modality of photodynamic therapy (PDT) through the design of our truly dual-functional—PDT and imaging—gadolinium complex (Gd-N), which can target cancer cells specifically. In the light of our design, the PDT drug can specifically localize on the anionic cell membrane of cancer cells in which its laser-excited photoemission signal can be monitored without triggering the phototoxic generation of reactive oxygen species—singlet oxygen—before due excitation. Comprehensive in vitro and in vivo studies had been conducted for the substantiation of the effectiveness of Gd-N as such a tumor-selective PDT photosensitizer. This treatment modality does initiate a new direction in the development of “precision medicine” in line with stem cell and gene therapies as tools in cancer therapy.