Associação Portuguesa de Investigação em Cancro
Porphyrin conjugated with monoclonal antibody anti-CD104 is a potential photosensitizer for bladder cancer treatment
Porphyrin conjugated with monoclonal antibody anti-CD104 is a potential photosensitizer for bladder cancer treatment
Photodynamic therapy (PDT) is a promising method, which has been studied and applied to improve the treatment of several tumour types. PDT combines molecular oxygen, light and a photosensitizer (PS) to generate cytotoxic reactions in cancer cells. The potential of PSs conjugated with biomolecules which will be recognized by antigens or receptors overexpressed in cancer cells prompted us to synthesize and to validate the photodynamic activity of a porphyrin conjugated with human and bovine serum albumins, and the monoclonal antibody anti-CD104. The photodynamic potential of the conjugates was evaluated by in vitro studies using the human bladder cancer cell line UM-UC-3. The conjugates demonstrated high efficacy in destroying the bladder cancer cells, with the mAb anti-CD104 efficacy overruling the albumin ones. The results demonstrated that the porphyrin conjugated with an antibody able to recognize the human antigen CD104 (which is overexpressed in bladder carcinomas) is a promising anticancer drug candidate for bladder cancer treatment.
Patrícia M. R. Pereira,a José J. Carvalho,b Sandrina Silva,a José A. S. Cavaleiro,aRudolf J. Schneider,*,b Rosa Fernandes,*,cand João P. C Tomé*,a,d
aQOPNA and Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal
bBAM Federal Institute for Materials Research and Testing, D-12489 Berlin, Germany
cIBILI and Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
dDepartment of Organic Chemistry, Ghent University, B-9000 Gent, Belgium
The synthesis of a novel PS conjugated with bovine and human serum albumin (BSA and HSA) and a monoclonal antibody anti-CD104 is reported, as well as their biological potential against the human bladder cancer cell line UM-UC-3. No photodynamic effect was detected when the non-conjugated porphyrin was used. Yet, when it was coupled covalently with the mAb anti-CD104, BSA and HSA, the resulting photosensitizer conjugates demonstrated high efficacy in destroying the cancer cells, the mAb anti-CD104 efficacy overruling the albumins.
Organic and Biomolecular Chemistry
http://pubs.rsc.org/en/content/articlelanding/2014/ob/c3ob42082e#!divAbstract
