Combined delivery of salinomycin and docetaxel by dual-targeting gelatinase nanoparticles effectively inhibits cervical cancer cells and cancer stem cells.
Combined delivery of salinomycin and docetaxel by dual-targeting gelatinase nanoparticles effectively inhibits cervical cancer cells and cancer stem cells.
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双靶向明胶酶纳米粒子联合递送盐霉素和多西紫杉醇可有效抑制宫颈癌细胞和癌症干细胞
DOI：
10.1080/10717544.2021.1886378
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发表时间：
2021-12
期刊：
影响因子：
6
通讯作者：
Liu B
中科院分区：
文献类型：
--
作者：
Wang Q;Yen YT;Xie C;Liu F;Liu Q;Wei J;Yu L;Wang L;Meng F;Li R;Liu B
摘要肿瘤内异质性是阻碍肿瘤患者完全康复的重要因素之一。特别是，癌症干细胞（CSCs）可能表现出自我更新能力，这使得完全消除肿瘤变得更加困难。因此，同时抑制肿瘤中的CSC和非CSC成为获得可持续抗癌功效的有前景的策略。盐霉素（Salinomycin，Sal）是抑制肿瘤干细胞的关键药物。但其生物利用度低、毒副作用大，限制了其临床应用。为了解决这个问题，我们先前构建了明胶酶刺激纳米颗粒，其由无毒的、生物相容的聚乙二醇-聚己内酯（PEG-PCL）共聚物组成，其中明胶酶可切割肽Pro-Val-Gly-Leu-Iso-Gly（PVGLIG）插入共聚物的两个嵌段之间。通过将我们的“智能”明胶酶响应性纳米颗粒应用于Sal递送，我们在先前的研究中已经证明了Sal-纳米颗粒在肿瘤中的特异性积累、抗CSC能力和降低的毒性。在本研究中，我们合成了Sal-Doc-loaded明胶酶刺激物纳米颗粒（Sal-Doc NP），并与纳米沉淀法相比，证实了单乳液法是制备Sal-Doc NP（Sal-Doc SE-NP）的最佳方法。Sal-Doc SE-NPs对宫颈癌移植小鼠的CSC和非CSC均有抑制作用，可能与增强上皮-间质转化（EMT）途径的限制有关。再攻击实验中，Sal-Doc-SE-NPs组的成瘤能力和生长速度明显受到抑制。我们的研究结果表明，Sal-Doc负载明胶酶刺激物纳米颗粒可能是一种有前途的策略，通过同时抑制CSC和非CSC来增强抗肿瘤疗效并减少副作用。
Abstract Intra-tumor heterogeneity is widely accepted as one of the key factors, which hinders cancer patients from achieving full recovery. Especially, cancer stem cells (CSCs) may exhibit self-renewal capacity, which makes it harder for complete elimination of tumor. Therefore, simultaneously inhibiting CSCs and non-CSCs in tumors becomes a promising strategy to obtain sustainable anticancer efficacy. Salinomycin (Sal) was reported to be critical to inhibit CSCs. However, the poor bioavailability and catastrophic side effects brought about limitations to clinical practice. To solve this problem, we previously constructed gelatinase-stimuli nanoparticles composed of nontoxic, biocompatible polyethylene glycol-polycaprolactone (PEG-PCL) copolymer with a gelatinase-cleavable peptide Pro-Val-Gly-Leu-Iso-Gly (PVGLIG) inserted between the two blocks of the copolymer. By applying our “smart” gelatinase-responsive nanoparticles for Sal delivery, we have demonstrated specific accumulation in tumor, anti-CSCs ability and reduced toxicity of Sal-NPs in our previous study. In the present study, we synthesized Sal-Docetaxel-loaded gelatinase-stimuli nanoparticles (Sal-Doc NP) and confirmed single emulsion as the optimal method of producing Sal-Doc NPs (Sal-Doc SE-NP) in comparison with nanoprecipitation. Sal-Doc SE-NPs inhibited both CSCs and non-CSCs in mice transplanted with cervical cancer, and might be associated with enhanced restriction of epithelial-mesenchymal transition (EMT) pathway. Besides, the tumorigenic capacity and growing speed were obviously suppressed in Sal-Doc-SE-NPs-treated group in rechallenge experiment. Our results suggest that Sal-Doc-loaded gelatinase-stimuli nanoparticles could be a promising strategy to enhance antitumor efficacy and reduce side effects by simultaneously suppressing CSCs and non-CSCs.
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明胶酶刺激策略增强多西紫杉醇负载的聚乙二醇-聚己内酯纳米颗粒的肿瘤递送和治疗效果
影响因子：
8
作者：
Liu Q;Li RT;Qian HQ;Yang M;Zhu ZS;Wu W;Qian XP;Yu LX;Jiang XQ;Liu BR
通讯作者：
Liu BR
DOI：
10.1073/pnas.1513433112
发表时间：
2015-08-18
影响因子：
11.1
作者：
Lu, Haiquan;Samanta, Debangshu;Semenza, Gregg L.
通讯作者：
Semenza, Gregg L.
负载多西紫杉醇的明胶酶刺激 PEG-Pep-PCL 纳米颗粒增强胃癌放疗效果。
影响因子：
9.7
作者：
Cui, Fang-bo;Li, Ru-Tian;Liu, Bao-Rui
通讯作者：
Liu, Bao-Rui
影响因子：
2.3
作者：
Li, Lan;Cui, Dejun;Cao, Yu
通讯作者：
Cao, Yu
影响因子：
5.8
作者：
Muntimadugu, Eameema;Kumar, Rajendra;Khan, Wahid
通讯作者：
Khan, Wahid