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Title:
PHOTOSENSITIZER-PEPTIDE CONJUGATE COMPRISING DEGRADABLE LINKER, AND COMPOSITION FOR PHOTODYNAMIC DIAGNOSIS OR TREATMENT COMPRISING SAME
Document Type and Number:
WIPO Patent Application WO/2018/012778
Kind Code:
A1
Abstract:
The present invention relates to a conjugate for photodynamic diagnosis or treatment in which a peptide binds with a photosensitizer via an intracellularly degradable linkage, and to a composition for photodynamic diagnosis or treatment comprising the same. The conjugate of the present invention generates no fluorescent signal and reactive oxygen in normal tissues or during the circulation in the blood by quenching a fluorescent signal and reactive oxygen production ability of the photosensitizer. After the conjugate is selectively absorbed into target cells, a linker is degraded in the cells to increase the distance between tryptophan contained in the peptide and the photosensitizer, and the quenching action is terminated to generate a strong fluorescence signal and induce active generation of reactive oxygen. Therefore, the conjugate according to the present invention has high tissue permeability, shows a high photodynamic therapeutic effect in only target cells while being safe in normal cells, and can obtain a good diagnostic image having a high ratio of target signal to background.

Inventors:
CHOI YONG-DOO (KR)
KIM JI-SU (KR)
Application Number:
PCT/KR2017/007068
Publication Date:
January 18, 2018
Filing Date:
July 04, 2017
Export Citation:
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Assignee:
NAT CANCER CT (KR)
International Classes:
A61K41/00; A61K38/17; A61K47/50; G01N33/544
Domestic Patent References:
WO2009046220A22009-04-09
Other References:
FONTENOT, K. R. ET AL.: "Targeting of t he Epidermal Growth Factor Receptor with Mesoporphyrin I X-peptide Conjugates", JOURNAL OF PORPHYRINS AND PHTHALOCYANINES, vol. 20, no. 01n04, January 2016 (2016-01-01), pages 352 - 366, XP009514433, ISSN: 1088-4246, DOI: 10.1142/S1088424616500115
KIM, H. ET AL.: "Photosensitizer-conjugated Polymeric Nanoparticles for Redox-responsive Fluorescence Imaging and Photodynamic Therapy", JOURNAL OF MATERIALS CHEMISTRY B, vol. 1, no. 4, 2013, pages 429 - 431, XP055456929
SALERNO, A. ET AL.: "Covalent Modification with Concomitant Inactivation of the cAMP-dependent Protein Kinase by Affinity Labels Containing Only L-amino Acids", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 268, no. 18, 1993, pages 13043 - 13049, XP000676507
KHANANSHVILI, D. ET AL.: "Positively Charged Cyclic Hexapeptides, Novel Blockers for the Cardiac Sarcolemma Na+-Ca2+ Exchanger", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 270, no. 27, 1995, pages 16182 - 16188, XP000676506
S CHMITT, F ET AL.: "Drug Targeting Strategies for Photodynamic Therapy", ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY, vol. 12, no. 5, May 2012 (2012-05-01), pages 500 - 525, XP055456935
KIM, J. ET AL.: "Photosensitizer-conjugated Tryptophan-containing Peptide Ligands as New Dual-targeted Theranostics for Cancers", INTERNATIONAL JOURNAL OF PHARMACEUTICS, vol. 513, no. 1, 26 September 2016 (2016-09-26), pages 584 - 590, XP029774144
KIM, J. ET AL.: "A Redox-responsive Theranostic Agent for Target-specific Fluorescence Imaging and Photodynamic Therapy of EGFR-overexpressing Triple-negative Breast Cancers", JOURNAL OF MATERIALS CHEMISTRY B, vol. 4, 13 September 2016 (2016-09-13), pages 6787 - 6790, XP055456938
Attorney, Agent or Firm:
WIE, Byoung-Gap (KR)
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