Wlodarczyk Marek T, Dragulska Sylwia A, Camacho-Vanegas Olga, Dottino Peter R, Jarzęcki Andrzej A, Martignetti John A, Mieszawska Aneta J
Department of Chemistry, Brooklyn College, The City University of New York, 2900 Bedford Avenue, Brooklyn NY 11210.
Ph.D. Program in Chemistry, The Graduate Center of the City University of New York, New York, NY 10016.
ACS Biomater Sci Eng. 2018 Feb 12;4(2):463-467. doi: 10.1021/acsbiomaterials.7b00921. Epub 2018 Jan 9.
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.
铂类疗法是许多恶性肿瘤的一线治疗方法，但其高全身毒性限制了治疗剂量。在此，我们报告了具有叠氮化物和炔烃官能团的卡铂类配合物的合成，以及铂（II）-核定位序列肽（Pt-NLS）杂化物的形成，以改善铂（II）配合物直接导入细胞核的过程。Pt-NLS杂化物成功进入细胞及其细胞核，形成铂诱导的核损伤。Pt-NLS的体外疗效很高，在相同浓度下优于天然卡铂。所使用的方法简单且具有成本效益，最重要的是可以很容易地扩展到将铂（II）负载到其他载体上，为增强铂（II）治疗的递送开辟了新的可能性。
