Photoactive platinum(IV) complex conjugated to a cancer-cell-targeting cyclic peptide

Huayun Shi; Qian Wang; V Venkatesh; Guokai Feng; Lawrence S Young; Isolda Romero-Canelón; Musheng Zeng; Peter J. Sadler

doi:10.1039/C9DT00909D

Photoactive platinum(IV) complex conjugated to a cancer-cell-targeting cyclic peptide

Huayun Shi, Qian Wang, V Venkatesh, Guokai Feng, Lawrence S Young, Isolda Romero-Canelón, Musheng Zeng, Peter J. Sadler

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Abstract

A conjugate of cancer-cell targeting cyclic disulphide nona-peptide c(CRWYDENAC) consisting of nine l-amino acids with the photoactive succinate platinum(iv) complex trans,trans-[Pt(N ₃) ₂(py) ₂(OH)(succinate)] (Pt-cP) has been synthesised and characterised. The conjugate was stable in dark, but released succinate-peptide and Pt(ii) species upon irradiation with visible light, and formed photoproducts with guanine. Conjugate Pt-cP exhibited higher photocytotoxicity than parent complex trans,trans,trans-[Pt(N ₃) ₂(OH) ₂(py) ₂] (FM-190) towards cancer cells, including ovarian A2780, lung A549 and prostate PC3 human cancer cells upon irradiation with blue light (465 nm, 17.28 J cm ^-2) with IC ₅₀ values of 2.8-22.4 μM and the highest potency for A549 cells. Even though the dark cellular accumulation of Pt-cP in A2780 cells was lower than that of parent FM-190, Pt from Pt-cP accumulated in cancer cells upon irradiation to a level >3× higher than that from FM-190. In addition, the cellular accumulation of Pt from Pt-cP was enhanced ca. 47× after irradiation.

Original language	English
Pages (from-to)	8560-8564
Number of pages	5
Journal	Dalton Transactions
Volume	48
Issue number	24
Early online date	31 May 2019
DOIs	https://doi.org/10.1039/C9DT00909D
Publication status	Published - 6 Aug 2019

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title = "Photoactive platinum(IV) complex conjugated to a cancer-cell-targeting cyclic peptide",

abstract = "A conjugate of cancer-cell targeting cyclic disulphide nona-peptide c(CRWYDENAC) consisting of nine l-amino acids with the photoactive succinate platinum(iv) complex trans,trans-[Pt(N 3) 2(py) 2(OH)(succinate)] (Pt-cP) has been synthesised and characterised. The conjugate was stable in dark, but released succinate-peptide and Pt(ii) species upon irradiation with visible light, and formed photoproducts with guanine. Conjugate Pt-cP exhibited higher photocytotoxicity than parent complex trans,trans,trans-[Pt(N 3) 2(OH) 2(py) 2] (FM-190) towards cancer cells, including ovarian A2780, lung A549 and prostate PC3 human cancer cells upon irradiation with blue light (465 nm, 17.28 J cm -2) with IC 50 values of 2.8-22.4 μM and the highest potency for A549 cells. Even though the dark cellular accumulation of Pt-cP in A2780 cells was lower than that of parent FM-190, Pt from Pt-cP accumulated in cancer cells upon irradiation to a level >3× higher than that from FM-190. In addition, the cellular accumulation of Pt from Pt-cP was enhanced ca. 47× after irradiation. ",

author = "Huayun Shi and Qian Wang and V Venkatesh and Guokai Feng and Young, {Lawrence S} and Isolda Romero-Canel{\'o}n and Musheng Zeng and Sadler, {Peter J.}",

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doi = "10.1039/C9DT00909D",

language = "English",

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T1 - Photoactive platinum(IV) complex conjugated to a cancer-cell-targeting cyclic peptide

AU - Shi, Huayun

AU - Wang, Qian

AU - Venkatesh, V

AU - Feng, Guokai

AU - Young, Lawrence S

AU - Romero-Canelón, Isolda

AU - Zeng, Musheng

AU - Sadler, Peter J.

PY - 2019/8/6

Y1 - 2019/8/6

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DO - 10.1039/C9DT00909D

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Photoactive platinum(IV) complex conjugated to a cancer-cell-targeting cyclic peptide

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