Photodynamic Efficiency: From Molecular Photochemistry to Cell Death.
Photodynamic therapy (PDT) is a clinical modality used to treat cancer and infectious diseases. The main agent is the photosensitizer (PS), which is excited by light and converted to a triplet excited state. This latter species leads to the formation of singlet oxygen and radicals that oxidize biomolecules. The main motivation for this review is to suggest alternatives for achieving high-efficiency PDT protocols, by taking advantage of knowledge on the chemical and biological processes taking place during and after photosensitization. We defend that in order to obtain specific mechanisms of cell death and maximize PDT efficiency, PSes should oxidize specific molecular targets. We consider the role of subcellular localization, how PS photochemistry and photophysics can change according to its nanoenvironment, and how can all these trigger specific cell death mechanisms. We propose that in order to develop PSes that will cause a breakthrough enhancement in the efficiency of PDT, researchers should first consider tissue and intracellular localization, instead of trying to maximize singlet oxygen quantum yields in in vitro tests. In addition to this, we also indicate many open questions and challenges remaining in this field, hoping to encourage future research.
Instituto de Química, Universidade de São Paulo, São Paulo 05508-900, Brazil. isabel@iq.usp.br.
Isabel O L
IO
Bacellar
Instituto de Química, Universidade de São Paulo, São Paulo 05508-900, Brazil. tayana_tmt@hotmail.com.
Tayana M
TM
Tsubone
Programa de Pós Graduação em Biofotônica Aplicada às Ciências da Saúde, Universidade Nove de Julho, São Paulo 01504-001, Brazil. chrispavani@uninove.br.
Christiane
C
Pavani
Instituto de Química, Universidade de São Paulo, São Paulo 05508-900, Brazil. baptista@iq.usp.br.
Mauricio S
MS
Baptista
D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D010084:Oxidation-Reduction / Q000187:drug effects / Q000528:radiation effects; D010777:Photochemistry; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology
D017319:Photosensitizing Agents
cell death; photodynamic therapy; photooxidation; photosensitization; subcellular localization