Peptide-targeted, stimuli-responsive polymersomes for delivering a cancer stemness inhibitor to cancer stem cell microtumors.
Peptide-targeted, stimuli-responsive polymersomes for delivering a cancer stemness inhibitor to cancer stem cell microtumors.
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DOI：
10.1016/j.colsurfb.2017.12.036
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发表时间：
2018-03-01
期刊：
影响因子：
--
通讯作者：
Mallik S
中科院分区：
文献类型：
--
作者：
Karandish F;Froberg J;Borowicz P;Wilkinson JC;Choi Y;Mallik S
由于肿瘤的异质性和可以更新的祖干细胞的存在，癌症通常会在对化疗产生初步反应后复发。为了克服癌症的耐药性、转移和复发，一种有前景的方法是抑制癌症干性。在这项研究中，鉴定了胰腺癌和前列腺癌干细胞中的 Neuropilin-1 受体的表达，并用刺激响应性聚合物纳米载体靶向，将干细胞抑制剂 (napabucasin) 递送至癌症干细胞。合成了还原敏感的两亲性嵌段共聚物PEG1900-S-S-PLA6000和N3-PEG1900-PLA6000。肿瘤穿透性 iRGD 肽-己炔酸缀合物通过 Cu2+ 催化的“点击”反应与 N3-PEG1900-PLA6000 聚合物连接。随后，这种肽-聚合物缀合物被掺入聚合物囊泡中，用于肿瘤靶向和组织渗透。我们制备了含有 85% PEG1900-S-S-PLA6000、10% iRGD-聚合物缀合物和 5% DPPE-丽丝胺罗丹明染料的聚合物囊泡。封装癌症干细胞抑制剂 napabucasin 的 iRGD 靶向聚合物囊泡内化于前列腺癌和胰腺癌干细胞中。与对照和不含任何药物的囊泡相比，napabucasin 封装的聚合物囊泡显着（p < 0.05）降低了前列腺癌和胰腺癌干细胞的活力，并降低了干细胞蛋白 notch-1 和 nanog 的表达。 napabucasin 封装的聚合物囊泡制剂有可能通过深入渗透到肿瘤中，释放封装的干细胞抑制剂并杀死癌症干细胞，从而引领前列腺癌和胰腺癌治疗的新方向。
Often cancer relapses after an initial response to chemotherapy because of the tumor’s heterogeneity and the presence of progenitor stem cells, which can renew. To overcome drug resistance, metastasis, and relapse in cancer, a promising approach is the inhibition of cancer stemness. In this study, the expression of the neuropilin-1 receptor in both pancreatic and prostate cancer stem cells was identified and targeted with a stimuli-responsive, polymeric nanocarrier to deliver a stemness inhibitor (napabucasin) to cancer stem cells. Reduction-sensitive amphiphilic block copolymers PEG1900-S-S-PLA6000 and the N3-PEG1900-PLA6000 were synthesized. The tumor penetrating iRGD peptide-hexynoic acid conjugate was linked to the N3-PEG1900-PLA6000 polymer via a Cu2+ catalyzed “Click” reaction. Subsequently, this peptide-polymer conjugate was incorporated into polymersomes for tumor targeting and tissue penetration. We prepared polymersomes containing 85% PEG1900-S-S-PLA6000, 10% iRGD-polymer conjugate, and 5% DPPE-lissamine rhodamine dye. The iRGD targeted polymersomes encapsulating the cancer stemness inhibitor napabucasin were internalized in both prostate and pancreatic cancer stem cells. The napabucasin encapsulated polymersomes significantly (p < 0.05) reduced the viability of both prostate and pancreatic cancer stem cells and decreased the stemness protein expression notch-1 and nanog compared to the control and vesicles without any drug. The napabucasin encapsulated polymersome formulations have the potential to lead to a new direction in prostate and pancreatic cancer therapy by penetrating deeply into the tumors, releasing the encapsulated stemness inhibitor, and killing cancer stem cells.
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影响因子：
4.2
作者：
Anajafi T;Mallik S
通讯作者：
Mallik S
影响因子：
4.1
作者：
Karandish, Fataneh;Haldar, Manas K.;You, Seungyong;Brooks, Amanda E.;Brooks, Benjamin D.;Guo, Bin;Choi, Yongki;Mallik, Sanku
通讯作者：
Mallik, Sanku
影响因子：
4.9
作者：
Anajafi, Tayebeh;Yu, Junru;Mallik, Sanku
通讯作者：
Mallik, Sanku
DOI：
10.1016/j.bbrc.2012.07.151
发表时间：
2012-09-07
影响因子：
3.1
作者：
Glinka, Yelena;Mohammed, Nada;Prud'homme, Gerald J.
通讯作者：
Prud'homme, Gerald J.
影响因子：
11.2
作者：
Gu, Guangyu;Yuan, Jialing;Kasper, Susan
通讯作者：
Kasper, Susan