Photoimmunoconjugates: novel synthetic strategies to target and treat cancer by photodynamic therapy

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Photoimmunoconjugates: novel synthetic strategies to target and treat cancer by photodynamic therapy

Wednesday, 10.04.2019

Photodynamic therapy (PDT) has evolved as a therapeutic modality in the treatment of various types of cancer. The destruction of tumor cells is due to the formation of reactive oxygen species resulting from the interaction between the photosensitizer (PS), light, and oxygen. Recently, the combination of the photosensitizer with antibodies, or with antibody fragments, has contributed to improvements in the specificity of this phototherapy, reducing its side effects. The photoimmunoconjugate binds specifically to a protein overexpressed by the cancer cells and it is then irradiated with light to generate reactive oxygen species that are toxic to the cancer cells. This mini-review, published as "advanced HOT article" in the journal "Organic & Biomolecular Chemistry," describes synthetic strategies by which an antibody is conjugated with a photosensitizer and it highlights the most recent preclinical and clinical studies using photoimmunoconjugates for the treatment of cancer by photodynamic therapy.

 

Authors and Affiliations:

Sara R. G. Fernandes,a,b,cRosa Fernandes,d,eBruno Sarmento,b,c,fPatrícia M. R. Pereira*g and João P. C. Tomé*a

aCQE, Departamento de Engenharia Química, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal.

bINEB - Instituto de Engenharia Biomédica, University of Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal

ci3S - Instituto de Investigação e Inovação em Saúde, University of Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal

dCoimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal

eCNC.IBILI Consortium, University of Coimbra, Portugal

fCESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Instituto Universitário de Ciências da Saúde, Rua Central de Gandra, 1317, 4585-116 Gandra, Portugal

gDepartment of Radiology, Memorial Sloan Kettering, New York, NY 10065, USA.

 

Abstract:

Photodynamic therapy (PDT) combines a photosensitizer (PS) with the physical energy of non-ionizing light to trigger cell death pathways. PDT has potential as a therapeutic modality to be used in alternative or in combination with other conventional cancer treatment protocols (e.g. surgery, chemotherapy and radiotherapy). Still, due to the lack of specificity of the current PSs to target the tumor cells, several studies have exploited their conjugation with targeting moieties. PSs conjugated with antibodies (Abs) or their fragments, able to bind antigens overexpressed in the tumors, have demonstrated potential in PDT of tumors. This review provides an overview of the most recent advances on photoimmunoconjugates (PICs) for cancer PDT, which involve the first and second-generation PSs conjugated to Abs. This is an update of our previous review “Antibodies armed with photosensitizers: from chemical synthesis to photobiological applications”, published in 2015 in Org. Biomol. Chem.

 

Journal: Organic & Biomolecular Chemistry

 

Link: https://pubs.rsc.org/en/content/articlelanding/2019/ob/c8ob02902d/unauth#!divAbstract