Genetically Engineered Nanoparticles of Asymmetric Triblock Polypeptide with a Platinum(IV) Cargo Outperforms a Platinum(II) Analog and Free Drug in a Murine Cancer Model.
Genetically Engineered Nanoparticles of Asymmetric Triblock Polypeptide with a Platinum(IV) Cargo Outperforms a Platinum(II) Analog and Free Drug in a Murine Cancer Model.
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DOI：
10.1021/acs.nanolett.2c01850
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发表时间：
2022-07-27
期刊：
影响因子：
10.8
通讯作者：
Chilkoti, Ashutosh
中科院分区：
文献类型：
--
作者：
Saha, Soumen;Banskota, Samagya;Liu, Jianqiao;Zakharov, Nikita;Dzuricky, Michael;Li, Xinghai;Fan, Ping;Deshpande, Sonal;Spasojevic, Ivan;Sharma, Kedar;Borgnia, Mario Juan;Schaal, Jeffrey L.;Raman, Ashutosh;Kim, Sarah;Bhattacharyya, Jayanta;Chilkoti, Ashutosh
尽管铂（Pt）药物被广泛用于癌症治疗，但其开发已陷入停滞，因为十多年来没有新的Pt药物被批准。将小分子药物包装成纳米颗粒是增强其治疗功效的一种方法。然而，在设计Pt纳米颗粒时的一个重要考虑因素，以及本研究的焦点，是Pt的氧化状态的合理选择。迄今为止，还没有直接比较在相同的纳米颗粒系统中选择Pt氧化态的相对优点，这将允许其最佳设计。为了解决这个缺陷，我们设计了一种重组不对称三嵌段多肽（ATBP），自组装成棒状胶束和螯合Pt（II）或使共价结合的Pt（IV）具有相似的形态和稳定性。ATBP-Pt（II）和ATBP-Pt（IV）纳米颗粒均使Pt的半衰期延长约45倍，但与ATBP-Pt（II）和顺铂相比，ATBP-Pt（IV）具有上级肿瘤消退功效。这些结果表明，将Pt（IV）装载到基因工程纳米颗粒中可能会产生新一代更有效的铂药物纳米制剂。
Despite the widespread use of platinum(Pt)-drugs for cancer-therapy, their development has stalled, as no new Pt-drugs have been approved in over a decade. Packaging small molecule drugs into nanoparticles is a way to enhance their therapeutic efficacy. However, an important consideration in designing Pt-nanoparticles, and the focus of this study, is the rational choice of oxidation-state of Pt. To date, there has been no direct comparison of relative merits of the choice of Pt oxidation-state in the same nanoparticle-system that would allow its optimal design. To address this lacuna, we designed an recombinant asymmetric triblock polypeptide (ATBP) that self-assembles into rod-shaped micelles and chelates Pt(II) or enable covalent conjugation of Pt(IV) with similar morphology and stability. Both ATBP-Pt(II) and ATBP-Pt(IV) nanoparticles enhanced the half-life of Pt by ~45-fold but ATBP-Pt(IV) had superior tumor regression efficacy compared to ATBP-Pt(II) and cisplatin. These results suggest loading Pt(IV) into genetically engineered nanoparticles may yield a new generation of more effective platinum-drug nanoformulations.
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DOI：
10.1093/jnci/djp079
发表时间：
2009-05-20
期刊：
Journal of the National Cancer Institute
影响因子：
--
作者：
Le Tourneau C;Lee JJ;Siu LL
通讯作者：
Siu LL
影响因子：
19
作者：
Bhattacharyya, Jayanta;Weitzhandler, Isaac;Chilkoti, Ashutosh
通讯作者：
Chilkoti, Ashutosh
影响因子：
2.8
作者：
Coluccia, Mauro;Natile, Giovanni
通讯作者：
Natile, Giovanni
DOI：
10.1039/c6dt01738j
发表时间：
2016-08-16
期刊：
Dalton transactions (Cambridge, England : 2003)
影响因子：
--
作者：
Basu U;Banik B;Wen R;Pathak RK;Dhar S
通讯作者：
Dhar S
DOI：
10.1007/978-1-60327-198-1_6
发表时间：
2011-01-01
期刊：
CHARACTERIZATION OF NANOPARTICLES INTENDED FOR DRUG DELIVERY
影响因子：
--
作者：
Clogston, Jeffrey D.;Patri, Anil K.
通讯作者：
Patri, Anil K.