A new anionic porphyrin-phosphate conjugate has been made as the substrate of phosphatase to evaluate its cellular-uptake
and potential targeting on cancer cells, taking advantage of the over-expression of phosphatases associated with
the development of cancers. The phosphate groups increase the hydrophilicity of porphyrin dityrosine phosphate and
facilitate its formulation in aqueous solvent. Upon hydrolysis by phosphatase after cellular uptaking, the more
hydrophobic porphyrin-dityrosine promises to give better cellular retention. Indeed, the phosphate conjugate displayed a
much better PDT effect than that of the parent porphyrin at the same concentration (10 &mgr;M) and light dosage on HeLa
cells, indicating the enzyme-cleavage reaction occurred in HeLa cells plays a role. Photosenzitizers utilizing enzyme-cleavage
might be a promising approach for photodynamic therapy.
Photodynamic therapy (PDT) is a method to treat cancer or non-cancer diseases by activation of the light-sensitive photosensitizers. Epstein Barr virus (EBV) has been implicated in the development of certain cancers such as nasopharyngeal carcinoma and B cell lymphoma. This study aims to examine the effects of EBV infection on the production of pro-inflammatory cytokines and chemokines in cells after the photosensitizer Zn-BC-AM PDT treatment. Epithelial tumor cell lines HONE-1 and latent EBV-infected HONE-1 (EBV-HONE-1) cells were used in this study. Cells were treated with the photosensitizer Zn-BC-AM for 24 hours before light irradiation. RT-PCR and quantitative ELISA methods were used for the evaluation of mRNA expression and production of cytokines, respectively. Results show that Zn-BC-AM PDT increases the production of IL-1a and IL-1b in EBV-HONE-1. Over a 10-fold increase in the production of IL-6 was observed in the culture supernatant of Zn-BC-AM PDT-treated HONE-1 cells. PDT-induced IL-6 production was observed in HONE-1 cells. EBV-HONE-1 has a higher background level of IL-8 production than the HONE-1. The production of IL-8 was suppressed in EBV-HONE-1cells after Zn-BC-AM PDT. Our results indicate that the response of HONE-1 cells to Zn-BC-AM PDT depends on the presence of latent EBV infection. Since IL-8 is a cytokine with angiogenic activity, Zn-BC-AM PDT may exert an anti-angiogenic effect through the suppression of IL-8 production by the EBV-infected cells.
As the PDT effect may be enhanced by localized hyperthermia (HT), it would be logical to find a single agent that could bring about these two modalities at precisely the target site for synergism. Since highly localized HT can be induced by magnetic field excitation of superparamagnetic nanoparticles, we report here the design and synthesis of photosensitizer-decorated iron oxide nanoparticles and their tumoricidal effect. Thus, a porphyrin is covalently anchored on the iron oxide nanoparticle via dihydroxybenzene which binds tightly on the surface of the nanoparticle by M-O bond. The morphology of the resultant nanoparticle was studied to show that the crystallinality is not changed and the nanoparticle remains superparamagnetic at room temperature. The conjugate is also strongly fluorescent indicating that the iron oxide hardly affects the optical properties of the surface bound porphyrin moieties. The conjugate is readily taken by cancer cell (Hela cell line) and is able to trigger apoptosis after excitation by light.
Ten trans-A2B and A3-type corrole photosensitizers carrying functional groups were synthesized and screened for PDT activities. Photocytotoxicity was measured by the MTT cell reduction assay on a cultured human nasopharyngeal carcinoma (NPC) cell line (HONE-1). Experimental results indicated that corroles containing a single hydroxyphenyl substituent (3, 4 and 5) exhibit the highest activity among the corrole derivatives investigated. Confocal microscopy revealed that the site of cellular localization of the photosensitizers is predominantly at mitochondria. Also, nuclear staining detected apoptotic cell death.
Nasopharyngeal carcinoma (NPC), endemic in Southern China, is ranked as the fourth leading cause of cancer deaths in Hong Kong. In an effort to develop new PDT agents for cancer treatment, with a particular emphasis on the NPC, we have investigated the benzochlorin-type photosensitizers. The chromophore is functionalized with side chains containing polar and/or cationic groups. Synthetic methods have been developed for such purposes; e.g. 5-chlorosulfonyloctaethylbenzochlorin and 5-bromooctaethylbenzochlorin are used as versatile precursors for the preparation of ammonium and amidinium salts. Preliminary in vitro study of the photodynamic activity of the synthetic compounds indicated that the cationic benzochlorin derivatives display significant photocytotoxicity towards NPC cells.
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