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一种光响应性铂-姜黄素复合物的合成、化学与生物学研究以及通过聚合物纳米颗粒递送至肿瘤细胞

Synthesis of a light-responsive platinum curcumin complex, chemical and biological investigations and delivery to tumor cells by means of polymeric nanoparticles.

作者信息

Vergaro Viviana, Dell'Anna Maria Michela, Shahsavari Hamid R, Baldassarre Francesca, Migoni Danilo, Mastrorilli Piero, Fanizzi Francesco Paolo, Ciccarella Giuseppe

机构信息

Biological and Environmental Sciences Department, UdR INSTM of Lecce University of Salento Via Monteroni 73100 Lecce Italy

Institute of Nanotechnology, CNR NANOTEC, Consiglio Nazionale delle Ricerche Via Monteroni 73100 Lecce Italy.

出版信息

Nanoscale Adv. 2023 Aug 30;5(19):5340-5351. doi: 10.1039/d3na00200d. eCollection 2023 Sep 26.

DOI:10.1039/d3na00200d
PMID:37767039
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10521244/
Abstract

Platinum-based anticancer drugs are common in chemotherapy, but problems such as systemic toxicity and acquired resistance of some tumors hamper their clinical applications and therapeutic efficacy. It is necessary to synthesize Pt-based drugs and explore strategies to reduce side effects and improve pharmacokinetic profiles. Photo-responsive chemotherapeutics have emerged as an alternative strategy against several cancers, as photoactivation offers spatial selectivity and fewer side effects. Here, we combine chemical synthesis and nanotechnology to create a multifunctional platinum drug delivery system based on the novel metal complex [Pt(ppy)(curc)] (ppy = deprotonated 2-phenylpyridine, curc = deprotonated curcumin)] embodying the naturally occurring bioactive molecule, curcumin. The ultrasonication method coupled with the layer-by-layer technology was employed to produce nanocolloids, which demonstrated a good biocompatibility, higher solubility in aqueous solution, stability, large drug loading, and good biological activity in comparison with the free drug. release experiments revealed that the polymeric nanoformulation is relatively stable under physiological conditions (pH = 7.4 and 37 °C) but sensitive to acidic environments (pH = 5.6 and 37 °C) which would trigger the release of the loaded drug. Our approach modifies the bioavailability of this Pt-based drug increasing its therapeutic action in terms of both cytotoxic and anti-metastasis effects.

摘要

铂类抗癌药物在化疗中很常见,但诸如全身毒性和某些肿瘤的获得性耐药等问题阻碍了它们的临床应用和治疗效果。有必要合成基于铂的药物,并探索减少副作用和改善药代动力学特征的策略。光响应性化疗药物已成为对抗多种癌症的一种替代策略,因为光激活具有空间选择性且副作用较少。在这里,我们结合化学合成和纳米技术,基于新型金属络合物[Pt(ppy)(curc)](ppy = 去质子化的2-苯基吡啶,curc = 去质子化的姜黄素)创建了一种多功能铂药物递送系统,该络合物包含天然存在的生物活性分子姜黄素。采用超声处理方法结合层层技术制备纳米胶体,与游离药物相比,该纳米胶体具有良好的生物相容性、在水溶液中更高的溶解度、稳定性、大载药量和良好的生物活性。释放实验表明,聚合物纳米制剂在生理条件(pH = 7.4和37°C)下相对稳定,但对酸性环境(pH = 5.6和37°C)敏感,这会触发所载药物的释放。我们的方法改变了这种基于铂的药物的生物利用度,在细胞毒性和抗转移作用方面增强了其治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0359/10521244/085e0b8af8a4/d3na00200d-f9.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0359/10521244/7f6aec4370f0/d3na00200d-s1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0359/10521244/08991b1b8563/d3na00200d-f1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0359/10521244/008af6935180/d3na00200d-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0359/10521244/69323b84f3a2/d3na00200d-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0359/10521244/e373e4182b1e/d3na00200d-f7.jpg
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本文引用的文献

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