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Platinum (II) complex-nuclear localization sequence peptide hybrid for overcoming platinum resistance in cancer therapy.

ABSTRACT: Platinum therapy represents first line of treatment in many malignancies but its high systemic toxicity limits the therapeutic dosage. Herein, we report the synthesis of carboplatin-like complexes with azide and alkyne functional groups and the formation of a platinum (II) - nuclear localization sequence peptide (Pt-NLS) hybrid to improve the import of platinum (II) complexes directly into the cell's nucleus. The Pt-NLS hybrid successfully enters cells and their nuclei, forming Pt-induced nuclear lesions. The in vitro efficacy of Pt-NLS is high, superior to native carboplatin at the same concentration. The methodology used is simple and cost-effective and most importantly can easily be extended to load the Pt (II) onto other supports, opening new possibilities for enhanced delivery of Pt (II) therapy.

SUBMITTER: Wlodarczyk MT 

PROVIDER: S-EPMC7009786 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Platinum (II) complex-nuclear localization sequence peptide hybrid for overcoming platinum resistance in cancer therapy.

Wlodarczyk Marek T MT   Dragulska Sylwia A SA   Camacho-Vanegas Olga O   Dottino Peter R PR   Jarzęcki Andrzej A AA   Martignetti John A JA   Mieszawska Aneta J AJ  

ACS biomaterials science & engineering 20180109 2

Platinum therapy represents first line of treatment in many malignancies but its high systemic toxicity limits the therapeutic dosage. Herein, we report the synthesis of carboplatin-like complexes with azide and alkyne functional groups and the formation of a platinum (II) - nuclear localization sequence peptide (Pt-NLS) hybrid to improve the import of platinum (II) complexes directly into the cell's nucleus. The Pt-NLS hybrid successfully enters cells and their nuclei, forming Pt-induced nuclea  ...[more]

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