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A discrete organoplatinum(II) metallacage as a multimodality theranostic platform for cancer photochemotherapy.

ABSTRACT: Photodynamic therapy is an effective alternative to traditional treatments due to its minimally invasive nature, negligible systemic toxicity, fewer side effects, and avoidance of drug resistance. However, it is still challenging to design photosensitizers with high singlet oxygen (¹O₂) quantum yields (QY) due to severe aggregation of the hydrophobic photosensitizers. Herein, we developed a discrete organoplatinum(II) metallacage using therapeutic cis-(PEt₃)₂Pt(OTf)₂ as the building block to improve the ¹O₂ QY, thus achieving synergistic anticancer efficacy. The metallacage-loaded nanoparticles (MNPs) with tri-modality imaging capability allow precise diagnosis of tumor and real-time monitoring the delivery, biodistribution, and excretion of the MNPs. MNPs exhibited excellent anti-metastatic effect and superior anti-tumor performance against U87MG, drug resistant A2780CIS, and orthotopic tumor models, ablating the tumors without recurrence after a single treatment. Gene chip analyses confirmed the contribution of different therapeutic modalities to the tumor abrogation. This supramolecular platform holds potential in precise cancer theranostics.

SUBMITTER: Yu G

PROVIDER: S-EPMC6194061 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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A discrete organoplatinum(II) metallacage as a multimodality theranostic platform for cancer photochemotherapy.

Yu Guocan G Yu Shan S Saha Manik Lal ML Zhou Jiong J Cook Timothy R TR Yung Bryant C BC Chen Jin J Mao Zhengwei Z Zhang Fuwu F Zhou Zijian Z Liu Yijing Y Shao Li L Wang Sheng S Gao Changyou C Huang Feihe F Stang Peter J PJ Chen Xiaoyuan X

Nature communications 20181018 1

Photodynamic therapy is an effective alternative to traditional treatments due to its minimally invasive nature, negligible systemic toxicity, fewer side effects, and avoidance of drug resistance. However, it is still challenging to design photosensitizers with high singlet oxygen (1O2) quantum yields (QY) due to severe aggregation of the hydrophobic photosensitizers. Herein, we developed a discrete organoplatinum(II) metallacage using therapeutic cis-(PEt3) ...[more]

PMID: 30337535

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Project description:A detailed mechanistic investigation of the thermal reactions of a series of bisphosphine alkylplatinum(II) enolate complexes is reported. The reactions of methylplatinum enolate complexes in the presence of added phosphine form methane and either free or coordinated enone, depending on the steric properties of the enone. Kinetic studies were conducted to determine the relationship between the rates and mechanism of beta-hydrogen elimination from enolate complexes and the rates and mechanism of beta-hydrogen elimination from alkyl complexes. The rates of reactions of the enolate complexes were inversely dependent on the concentration of added phosphine, indicating that beta-hydrogen elimination from the enolate complexes occurs after reversible dissociation of a phosphine. A normal, primary kinetic isotope effect was measured, and this effect was consistent with rate-limiting beta-hydrogen elimination or C-H bond-forming reductive elimination to form methane. Reactions of substituted enolate complexes were also studied to determine the effect of the steric and electronic properties of the enolate complexes on the rates of beta-hydrogen elimination. These studies showed that reactions of the alkylplatinum enolate complexes were retarded by electron-withdrawing substituents on the enolate and that reactions of enolate complexes possessing alkyl substituents at the beta-position occurred at rates that were similar to those of complexes lacking alkyl substituents at this position. Despite the trend in electronic effects on the rates of reactions of enolate complexes and the substantial electronic differences between an enolate and an alkyl ligand, the rates of decomposition of the enolate complexes were similar to those of the analogous alkyl complexes. To the extent that the rates of reaction of the two types of complexes are different, those involving beta-hydrogen elimination from the enolate ligand were faster. A difference between the rate-determining steps for decomposition of the two classes of complexes and an effect of stereochemistry on the selectivity for beta-hydrogen elimination are possible origins of the observed phenomena.

Dataset Information

A discrete organoplatinum(II) metallacage as a multimodality theranostic platform for cancer photochemotherapy.

Publications

A discrete organoplatinum(II) metallacage as a multimodality theranostic platform for cancer photochemotherapy.

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