Trap and kill strategy for non-BRCA mutant pancreatic cancer by co-delivery of olaparib and JQ1 with plectin-1 targeting peptide nanoparticles
Trap and kill strategy for non-BRCA mutant pancreatic cancer by co-delivery of olaparib and JQ1 with plectin-1 targeting peptide nanoparticles
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通过将奥拉帕尼和 JQ1 与 plectin-1 靶向肽纳米粒子共同递送来捕获和杀死非 BRCA 突变胰腺癌的策略
DOI：
10.1016/j.nantod.2020.100877
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发表时间：
2020-08
期刊：
影响因子：
17.4
通讯作者：
杨尹默
中科院分区：
文献类型：
--
作者：
杨尹默
聚腺苷二磷酸核糖聚合酶（poly（ADP-ribose）polymerase，PARP）抑制剂奥拉帕尼（olaparib，奥拉）可抑制DNA单链断裂的修复，最近已被美国食品药品监督管理局（FDA）批准用于治疗BRCA（Breast Cancer）突变的晚期胰腺癌患者。然而，非BRCA突变的胰腺癌患者对奥拉治疗的反应仍然不理想。迫切需要为大多数胰腺患者开发有效的治疗方案。最近，奥拉和同源重组抑制剂JQ 1的药物组合治疗非BRCA突变胰腺癌显示出有希望的结果。本文利用肽纳米颗粒平台的高载药量、良好的药代动力学特性和肽靶向基序的整合等优点，开发了一种专门设计的靶向肽纳米颗粒（PTNPs），用于联合递送奥拉和JQ 1治疗非BRCA突变型胰腺癌。我们证实，大多数胰腺肿瘤细胞是plectin-1阳性。PTNPs在体外可有效靶向plectin-1阳性胰腺肿瘤细胞，并在体内肿瘤部位有明显的蓄积。奥拉和JQ 1的靶向共递送诱导了更多的胰腺肿瘤细胞凋亡，并显著增强了原位和患者来源的异种移植物（PDX）模型中奥拉和JQ 1的联合治疗的协同效应。此外，这种高度协调的药物向肿瘤细胞的精确递送明显降低了由奥拉和JQ 1的组合引起的副作用。
The poly (ADP-ribose) polymerase (PARP) inhibitor olaparib (Ola), which inhibits the repair of DNA single-strand breaks, has been approved recently by the Food and Drug Administration (FDA) of U.S. for treatment of advanced pancreatic cancer patients withBRCA(Breast Cancer) mutations. However, the response of the pancreatic cancer patients with non-BRCAmutant to Ola treatment remains suboptimal. There is an urgent need to develop effective therapeutic solutions for the majority pancreatic patients. Recently, the drug combination of Ola and the homologous recombination inhibitor JQ1 to treat non-BRCAmutant pancreatic cancers has showed promising outcomes. Herein, we took the advantage of peptide nanoparticle platform, which possesses high drug loading capacity, desirable pharmacokinetic profiles and integration of peptide targeting motif, and developed a tailor-designed plectin-1 targeting peptide nanoparticles (PTNPs) for co-delivery of Ola and JQ1 to treat non-BRCAmutant pancreatic cancers. We confirmed that the majority pancreatic tumor cells are plectin-1 positive. The PTNPs efficiently targeted plectin-1 positive pancreatic tumor cellsin vitroand significantly accumulated in tumor sitein vivo. The targeted co-delivery of Ola and JQ1 induced much more pancreatic tumor cell apoptosis and significantly enhanced the synergistic effect of combination treatment of Ola and JQ1 in both orthotopic and patient-derived xenograft (PDX) models. Furthermore, this precise delivery of highly coordinated drugs to tumor cells distinctly reduced adverse effects caused by combination of Ola and JQ1.
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DOI：
10.1038/s41571-018-0114-z
发表时间：
2019-03
期刊：
Nature reviews. Clinical oncology
影响因子：
--
作者：
Pilié PG;Tang C;Mills GB;Yap TA
通讯作者：
Yap TA
影响因子：
8.8
作者：
Karakashev S;Zhu H;Yokoyama Y;Zhao B;Fatkhutdinov N;Kossenkov AV;Wilson AJ;Simpkins F;Speicher D;Khabele D;Bitler BG;Zhang R
通讯作者：
Zhang R
影响因子：
8.8
作者：
Bolden JE;Tasdemir N;Dow LE;van Es JH;Wilkinson JE;Zhao Z;Clevers H;Lowe SW
通讯作者：
Lowe SW
表皮生长因子受体靶向肽纳米颗粒同时递送吉西他滨和奥拉帕尼治疗伴有乳腺癌 2 (BRCA2) 突变的胰腺癌
影响因子：
17.1
作者：
Du, Chong;Qi, Yingqiu;Yang, Yinmo
通讯作者：
Yang, Yinmo
DOI：
10.1016/j.jconrel.2013.12.037
发表时间：
2014-03
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Ying Zhao;T. Ji;Hai Wang;Suping Li;Yuliang Zhao;Guangjun Nie
通讯作者：
Ying Zhao;T. Ji;Hai Wang;Suping Li;Yuliang Zhao;Guangjun Nie