In the last decades, several applications of photodynamic therapy (PDT) have been proposed, including the treatment of cancerous and non-cancerous diseases as well as antimicrobial infections. The therapy is based on the administration of a photosensitizing agent (PS) which, after activation with visible light, exerts cytotoxicity via production of highly reactive oxygen species (ROS) that cause photo-oxidative damages in the cellular sites of PS accumulation and as a consequence cell death. We studied porphyrins and porphyrin-derivatives to explore their potential usefulness for cancer and antimicrobial PDT; in particular we explored strategies for improving the efficiency and the selectivity of PDT in killing cancer cells and bacteria. In this study we evaluate the delivery to cancer cells of PSs conjugated to cationic antimicrobial peptides (CAMPs). CAMPs are known to exert antibacterial activity against selected bacteria but they also exhibit several features typical of cell-penetrating peptides (CPPs) largely studied as carriers of anticancer drugs. Some of the CAMPs appear also to exert selective anticancer activity. Based on this, we are studying CAMPs as new class of carriers for the delivery of PSs for tumour PDT. We are evaluating, in cancer cells in vitro, the selectivity of uptake and the efficiency of the delivery of the PS 5(4’-carboxyphenyl)-10,15,20-triphenylporphyrin (cTPP) conjugated to selected CAMPs (Buforin II, Magainin II, Apidaecin). Preliminary experiments in A549 lung epithelial cancer cells revealed that the intracellular delivery of cTPP conjugated to Buforin II or Magainin II was increased about tenfold and thirtyfold, respectively, with respect to the un-conjugated form of the PS, after 5 h of cell incubation. Therefore, when cells were irradiated with 1.5 J cm-2 of blue light, comparable photo-killing efficiencies were measured with the cTPP-conjugates using concentrations at least 10 times lower than those used for the un-conjugated porphyrin. Notwithstanding the greater improvement of PDT outcomes measured in A549 cells using CAMPs-porphyrin conjugates, further investigations are needed in order to determine the interactions of the drug conjugates with non-cancerous cells and to assess that the mechanisms of action of these CPPs in driving the delivery of the PS increases the efficiency and selectivity of the PDT treatment.

Cationic antimicrobial peptides as carriers of photosensitizers for photodynamic therapy of tumours

MORET, FRANCESCA;GOBBO, MARINA;CELOTTI, LUCIA;REDDI, ELENA
2013

Abstract

In the last decades, several applications of photodynamic therapy (PDT) have been proposed, including the treatment of cancerous and non-cancerous diseases as well as antimicrobial infections. The therapy is based on the administration of a photosensitizing agent (PS) which, after activation with visible light, exerts cytotoxicity via production of highly reactive oxygen species (ROS) that cause photo-oxidative damages in the cellular sites of PS accumulation and as a consequence cell death. We studied porphyrins and porphyrin-derivatives to explore their potential usefulness for cancer and antimicrobial PDT; in particular we explored strategies for improving the efficiency and the selectivity of PDT in killing cancer cells and bacteria. In this study we evaluate the delivery to cancer cells of PSs conjugated to cationic antimicrobial peptides (CAMPs). CAMPs are known to exert antibacterial activity against selected bacteria but they also exhibit several features typical of cell-penetrating peptides (CPPs) largely studied as carriers of anticancer drugs. Some of the CAMPs appear also to exert selective anticancer activity. Based on this, we are studying CAMPs as new class of carriers for the delivery of PSs for tumour PDT. We are evaluating, in cancer cells in vitro, the selectivity of uptake and the efficiency of the delivery of the PS 5(4’-carboxyphenyl)-10,15,20-triphenylporphyrin (cTPP) conjugated to selected CAMPs (Buforin II, Magainin II, Apidaecin). Preliminary experiments in A549 lung epithelial cancer cells revealed that the intracellular delivery of cTPP conjugated to Buforin II or Magainin II was increased about tenfold and thirtyfold, respectively, with respect to the un-conjugated form of the PS, after 5 h of cell incubation. Therefore, when cells were irradiated with 1.5 J cm-2 of blue light, comparable photo-killing efficiencies were measured with the cTPP-conjugates using concentrations at least 10 times lower than those used for the un-conjugated porphyrin. Notwithstanding the greater improvement of PDT outcomes measured in A549 cells using CAMPs-porphyrin conjugates, further investigations are needed in order to determine the interactions of the drug conjugates with non-cancerous cells and to assess that the mechanisms of action of these CPPs in driving the delivery of the PS increases the efficiency and selectivity of the PDT treatment.
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11577/2687924
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact