This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Photodynamic therapy (PDT) which uses light-activated drugs to target and destroy cancerous tumor cells has been receiving great attention. The advantage of such treatment is its ability to offer a localized form of therapy, thus, many side effects associated with chemotherapy can be eliminated. Porphyrins are one of the most useful photosensitizers. They trace tumors and accumulate around tumors and finally kill tumor cells upon initiation of a photophysical process. To maximize the PDT effect on subcutaneous tumors, a new generation of drugs must be developed that possess excellent delivery properties and that absorb photons efficiently. We seek to develop a novel class of new porphyrin photosensitizers that are expected to exhibit such desirable properties. The present porphyrins are designed to possess a PDT prodrug, 5-aminolevuinic acid (ALA), a precursor to the PDT drug protoporphyrin IX (PpIX). They will be also furnished with motif groups such as carbohydrates that can specifically target tumors. This approach is to unite the strength of both PDT active ingredients, achieve desirable delivery property, and maximize drug effect. Moreover, porphyrins will be further annexed with electron-withdrawing groups. This strategy is utilized to achieve NIR absorption and a high absorption coefficient. The use of a conjugation pathway is anticipated to improve these properties. Therefore, new classes of porphyrin drugs are expected to possess superior delivery property, superior photosensitizing property, and superior PDT effect.
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