HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Photoinduced cytotoxicity and biodistribution of prostate cancer cell-targeted porphyrins.

Abstract
A series of five porphyrin-peptide conjugates bearing one or two sequences containing a cell penetrating peptide (CPP), a nuclear localization signal (NLS), or a bifunctional CPP-NLS or NLS-CPP sequences were synthesized and investigated in vitro using PC-3M human prostate cancer cells, in comparison with FDA-approved purified hematoporphyrin derivative (Porfimer Sodium) and mTHPC. The most promising porphyrin-HIV-1 Tat (48-60) conjugate 2 [lowest dark cytotoxicity (IC50 = 38.0 microM), highest phototoxicity (IC50 = 0.40 microM at 1 J/cm2)] was further evaluated in an in vivo biodistribution study using SCID mice bearing PC-3M tumors, in comparison with purified hematoporphyrin derivative. Porphyrin conjugate 2 was more tumor selective than the hematoporphyrin derivative and accumulated to a significantly greater extent in tumors. Our results show that effective photodynamic cytotoxicity can be induced in human prostate cancer cells with minimal dark toxicity and that selective accumulation in prostate tumors can be achieved in vivo with porphyrin-targeted photosensitizers.
AuthorsInder Sehgal, Martha Sibrian-Vazquez, M Graça H Vicente
JournalJournal of medicinal chemistry (J Med Chem) Vol. 51 Issue 19 Pg. 6014-20 (Oct 09 2008) ISSN: 1520-4804 [Electronic] United States
PMID18839477 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • Mesoporphyrins
  • Peptides
  • Photosensitizing Agents
  • Porphyrins
  • Dihematoporphyrin Ether
  • temoporfin
Topics
  • Animals
  • Cell Survival (drug effects, radiation effects)
  • Dihematoporphyrin Ether (pharmacology, radiation effects)
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Light
  • Lysosomes (drug effects)
  • Male
  • Mesoporphyrins (pharmacology, radiation effects)
  • Mice
  • Mice, SCID
  • Molecular Structure
  • Peptides (chemistry, pharmacology, radiation effects)
  • Photochemistry
  • Photochemotherapy (methods)
  • Photosensitizing Agents (chemistry, pharmacology, radiation effects)
  • Porphyrins (chemistry, pharmacology, radiation effects)
  • Prostatic Neoplasms (drug therapy, metabolism, pathology)
  • Stereoisomerism
  • Time Factors
  • Tissue Distribution
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: