Article

Pentalysine beta-Carbonylphthalocyanine Zinc: An Effective Tumor-Targeting Photosensitizer for Photodynamic Therapy (vol 5, pg 890, 2010)

Graduate University of Chinese Academy of Sciences, 19 Yuquan Road, Shijingshan District, Beijing 100049, China.
ChemMedChem (Impact Factor: 3.05). 06/2010; 5(6):890-8. DOI: 10.1002/cmdc.201000042
Source: PubMed

ABSTRACT Unsymmetrical phthalocyanine derivatives have been widely studied as photosensitizers for photodynamic therapy (PDT), targeting various tumor types. However, the preparation of unsymmetrical phthalocyanines is always a challenge due to the presence of many possible structural isomers. Herein we report a new unsymmetrical zinc phthalocyanine, pentalysine beta-carbonylphthalocyanine zinc (ZnPc-(Lys)(5)), that was prepared in large quantity and high purity. This is a water-soluble cationic photosensitizer and maintains a high quantum yield of singlet oxygen generation similar to that of unsubstituted zinc phthalocyanine (ZnPc). Compared with anionic ZnPc counterparts, ZnPc-(Lys)(5) shows a higher level cellular uptake and 20-fold higher phototoxicity toward tumor cells. Pharmacokinetics and PDT studies of ZnPc-(Lys)(5) in S180 tumor-bearing mice showed a high ratio of tumor versus skin retention and significant tumor inhibition. This new molecular framework will allow synthetic diversity in the number of lysine residues incorporated and will facilitate future QSAR studies.

0 Followers
 · 
129 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In the last decades the worldwide rise in antibiotic resistance has intensified the development of new antimicrobial agents. Photodynamic antimicrobial chemotherapy (PACT) has been used successfully to inactivate bacteria. We herein report a new zinc phthalocyanine based photosensitizer conjugated with polylysine moiety (ZnPc-PL). This photosensitizer significantly inactivated Porphyromonas gingivalis, the primary pathogenic bacteria responsible for periodontitis. No obvious phototoxicity was found to either mammalian bone marrow stromal cells (BMSC) or human periodontal ligament cells (HPDLC), indicating the high selectivity of ZnPc-PL toward bacteria. Furthermore, we established an experimental periodontitis model on beagle dogs to test the antimicrobial efficacy in vivo. The amount of gingival crevicular fluid (GCF) and the activity of crevicular fluid aspartate aminotransferase (AST) were monitored and were found to reduce significantly in the ZnPc-PL treated group compared to the controls (laser only and no treatment). In addition, PACT with ZnPc-PL caused a reduction in the bacterial burden by 100-fold compared to controls. Taken together, these findings suggest ZnPc-PL is a promising antimicrobial photosensitizer for the treatment of periodontal diseases.
    Journal of Porphyrins and Phthalocyanines 04/2011; 15(4):293-299. DOI:10.1142/S1088424611003276 · 1.36 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Photodynamic therapy (PDT) has attracted strong interest in the treatment of cancer due to the increased incidence of multidrug resistance and systemic toxicity in conventional chemotherapy. Phthalocyanine (Pc) is one of main classes of photosensitizers for PDT with optimal photophysical and photochemical properties. A higher specificity can ideally be achieved when Pcs are targeted towards tumor specific receptors, which may also facilitate specific drug delivery. Herein, we develop a simple and unique strategy to prepare a hydrophilic tumor-targeting photosensitizer ATF-ZnPc by covalently coupling zinc phthalocyanine (ZnPc) to the amino-terminal fragment (ATF) of urokinase-type plasminogen activator (uPA), a fragment responsible for uPA receptor (uPAR, a biomarker over-expressed in cancer cells), through the carboxyl groups of ATF. We demonstrate the high efficacy of such tumor-targeting PDT agent for the inhibition of tumor growth both in vitro and in vivo. Our in vivo optical imaging results using H22 tumor-bearing mice show clearly the selective accumulation of ATF-ZnPc in tumor region, thereby revealing the great potential of ATF-ZnPc for clinical applications such as cancer detection and guidance of tumor resection in addition to photodynamic treatment.
    Acta Biomaterialia 06/2014; 10(10):4257-4268. DOI:10.1016/j.actbio.2014.06.026 · 5.68 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The in vitro phototoxicity of a photostable, synthetic, water-soluble, halogenated bacteriochlorin, 5,10,15,20-tetrakis(2-chloro-5-sulfophenyl)bacteriochlorin (TCPBSO3H), toward mouse melanoma (S91) cells is ∼60-fold higher than that of the analogous porphyrin, and is associated with very weak toxicity in the dark; 90% of S91 cells were killed in response to a light dose of 0.26 J cm(-2) in the presence of [TCPBSO3H]=5 μM. In vivo toxicity toward DBA mice is very low, even at doses of 20 mg kg(-1). In vivo pharmacokinetics and biodistribution of TCPBSO3H were studied in DBA mice with S91 tumors; 24 h after intraperitoneal injection of 10 mg kg(-1), TCPBSO3H demonstrated preferential accumulation in S91 mouse melanoma, with tumor-to-normal tissue ratios of 3 and 5 for muscle and skin, respectively. Photodynamic therapy (PDT) performed under these conditions, with 90 mW cm(-2) diode laser irradiation at λ 750 nm for 20 min (total light dose of 108 J cm(-2)), resulted in tumor regression. Tumor recurrence was observed only approximately two months after treatment, confirming the efficacy of this PDT against melanoma.
    ChemMedChem 03/2011; 6(3):465-75. DOI:10.1002/cmdc.201000524 · 3.05 Impact Factor