A zinc(II) phthalocyanine conjugated with an oxaliplatin derivative for dual chemo- and photodynamic therapy.
A novel zinc(II) phthalocyanine substituted with an oxaliplatin derivative via a triethylene glycol linker has been synthesized. The two components work in a cooperative manner in the antitumor action. The conjugate shows a cytotoxic effect in the dark due to the cytostatic oxaliplatin moiety and an enhanced cytotoxicity upon illumination due to the photosensitizing phthalocyanine unit against the HT29 human colon adenocarcinoma cells. The IC(50) value of the conjugate is as low as 0.11 μM, which is 5-fold lower than that of the reference compound without the platinum complex. The high photodynamic activity of the conjugate can be attributed to its high cellular uptake and efficiency in generating intracellular reactive oxygen species. The conjugate also shows preferential localization in the lysosomes of the cells and induces cell death mainly through apoptosis.
Department of Chemistry, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China.
Janet T F
JT
Lau
Pui-Chi
PC
Lo
Wing-Ping
WP
Fong
Dennis K P
DK
Ng
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D019073:HT29 Cells; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D054833:Isoindoles; D008247:Lysosomes / Q000378:metabolism; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013329:Structure-Activity Relationship; D015032:Zinc
D000970:Antineoplastic Agents; D056831:Coordination Complexes; D007211:Indoles; D054833:Isoindoles; D009944:Organoplatinum Compounds; D017319:Photosensitizing Agents; D011725:Pyridines; D017382:Reactive Oxygen Species; C431073:oxiplatin; D015032:Zinc; C013647:phthalocyanine