Konjugati porfirina u fotodinamičkoj terapiji

Karcinom je i dalje vodeći uzrok smrti na globalnoj razini, bez obzira na napredak u liječenju i detekciji istih. Konvencionalni kemoterapeutski agensi korišteni u liječenju tumora su nespecifične toksičnosti te osim tumorskih, napadaju i zdrave stanice što dovodi do raznih nuspojava. Nadalje, tumorske stanice mogu nakon nekog vremena razviti rezistenciju na kemoterapeutike. Stoga, potreba za novim protutumorskim pristupima svakodnevno raste. Jedan od obećavajućih pristupa je fotodinamička terapija. Ova terapija kombinira zasebno tri netoksične komponente: kisik, fotosenzibilizator i svjetlost. Ozračivanjem fotosenzibilizatora svjetlošću odgovarajuće valne duljine u blizini molekularnog kisika dolazi do stvaranja visoko reaktivnog i toksičnog singlet kisika. Potonji može uzrokovati oksidativno oštećenje tkiva u kojem se nalazi. Stoga je vrlo bitno da se fotosenzibilizator lokalizira isključivo u tumorsko tkivo kako ne bi došlo do oštećenje zdravog tkiva. U tom pogledu, kao najučinkovitiji spojevi su se pokazali upravo porfirini. Veliki utjecaj na specifičnost porfirina ima njegova topljivost, tumorska distribucija i mogućnost prolaska kroz tumorsku membranu. Navedena specifičnost se pokušavala povećati na brojne načine, no kao najefikasniji način se pokazala konjugacija porfirina s određenim biomolekulama. Zbog lake dostupnosti i jednostavnog modificiranja, peptidi su se pokazali kao izvrsni vektori za konjugaciju. U ovom radu je prikazana konjugacija porfirina s antimikrobnim peptidom nizinom. Očekuje se da će amfipatska svojstva konjugata i prisutnost nizina u strukturi pospješiti topljivost fotosenzibilizatora i njegovo prodiranje kroz tumorsku membranu. Navedeno pozitivno utječe na specifičnost i efikasnost fotosenzibilizatora, a time i same fotodinamičke terapije.Carcinoma is still the leading cause of death globally, regardless of progress in their treatments and detection. Conventional chemotherapeutic agents used in the treatment of tumors have non-specific toxicity. Apart from tumor, they are attacking healthy cells as well, which leads to various side effects. Furthermore, tumor cells may eventually develop resistance to chemotherapy. Therefore, the need for new antitumor approaches is increasing every day. One of the promising approaches is photodynamic therapy. This therapy combines separately three nontoxic components: oxygen, photosensitizer and light. After the photosensitizer is irradiated with the light of the appropriate wavelength in the presence of the molecular oxygen, a highly reactive and toxic singlet oxygen is created. The latter can cause oxidative damage to the tissue in which it is present. Therefore, it is very important that the photosensitizer is localized solely in the tumor tissue so as to avoid damaging the healthy tissue. In this respect, so far the most effective compounds were porphyrins. Solubility, distribution within tumor and the ability to pass through the tumor membrane greatly influence the specificity of a porphyrin. There were different efforts to increase mentioned specificity, but the most efficient way was shown to be conjugation of porphyrin with certain biomolecules. Peptides are easily accessible and can be simply modified, and because of that they are proved to be excellent conjugation vectors. In this work, the conjugation of porphyrin with antimicrobial peptide nisin is shown. Amphiphilic properties of the conjugate and the presence of nisin in its structure are expected to enhance solubility of the photosensitizer and its penetration through the tumor membrane. This can positively affect the specificity and efficiency of the photosensitizer, thus photodynamic therapy itself