Furin-responsive triterpenine-based liposomal complex enhances anticervical cancer therapy through size modulation.
Furin-responsive triterpenine-based liposomal complex enhances anticervical cancer therapy through size modulation.
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弗林蛋白酶响应性三萜脂质体复合物通过尺寸调节增强抗宫颈癌治疗
DOI：
10.1080/10717544.2020.1827086
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发表时间：
2020-12
期刊：
影响因子：
6
通讯作者：
Chen Y
中科院分区：
文献类型：
--
作者：
Chen Y;Guo M;Qu D;Liu Y;Guo J;Chen Y
抗肿瘤药物在肿瘤组织中的蓄积和渗透与其抗肿瘤作用直接相关。纳米给药系统的粒径大小是影响抗肿瘤药物在肿瘤组织中蓄积和渗透的重要因素之一。通常，中等尺寸（100-120 nm）的纳米递送系统由于延长的循环和增强的渗透性和保留（EPR）效应而能够有效地积累;然而，较小尺寸（20-40 nm）的纳米递送系统对于肿瘤组织内的深度渗透是有效的。目前，常规的药物递送系统不能同时具有两种类型的最佳尺寸。为了解决这一问题并提高宫颈癌的治疗效果，开发了一种基于弗林蛋白酶响应性三萜碱的脂质体复合物（PEG可裂解的Tf-CTM/L），其核心为Tf-CTM（转铁蛋白修饰的雷公藤红素负载的薏苡仁油微乳液），包覆有热敏脂质和一种用弗林蛋白酶可裂解肽修饰的PEG壳，以提高肿瘤特异性积聚和渗透。在此，PEG可切割的Tf-CTM/L由于EPR效应而能够有效地积累。PEG壳层在过表达的弗林蛋白酶的刺激下能够及时脱落，解决了空间位阻难题。在宫颈癌中，小尺寸的Tf-CTM在肿瘤低温环境的刺激下释放，这对于在肿瘤部位的深度渗透是有效的。值得注意的是，与单独使用三萜相比，PEG可裂解的Tf-CTM/L通过有效积累和肿瘤组织内抗肿瘤药物的深度渗透而促进抗肿瘤功效并显示出降低的全身毒性。我们的研究提供了一种新的策略，并为抗宫颈癌治疗提供了有希望的潜力。
The accumulation and penetration of antitumor drugs in tumor tissues are directly related to their antitumor effects. The particle size of the nanodrug delivery system is one of the most important factors for the accumulation and penetration of antitumor drugs within tumor tissues. Generally, nanodelivery systems of intermediate size (100–120 nm) are capable of efficient accumulation owing to prolonged circulation and enhanced permeability and retention (EPR) effect; however, smaller ones (20–40 nm) are effective for deep penetration within tumor tissue. Currently a conventional drug delivery system cannot possess two types of optimal sizes, simultaneously. To solve this and to enhance cervical cancer treatment, a furin-responsive triterpenine-based liposomal complex (PEGcleavable Tf-CTM/L), with Tf-CTM (transferrin-modified tripterine-loaded coix seed oil microemulsion) in core, coated with a thermo-sensitive lipid and a kind of PEG shell modified with a furin-cleavable peptide was developed to improve tumor-specific accumulation and penetration. Herein, PEGcleavable Tf-CTM/L was capable of efficient accumulation because of EPR effect. The PEG shells could timely detach under stimulation of overexpressed furin protein to solve the problem of the steric hindrance dilemma. The small-sized Tf-CTM released under stimulation of tumor microthermal environment in cervical cancer, which was efficient with regards to deep penetration at tumor sites. Notably, compared to the use of triterpenine alone, PEGcleavable Tf-CTM/L promoted anticervical efficacy and displayed diminished systemic toxicity by efficient accumulation and deep penetration of antitumor drugs within tumor tissues. Our study provides a new strategy, and holds promising potential for anticervical cancer treatment.
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影响因子：
--
作者：
Kenechukwu FC;Attama AA;Ibezim EC;Nnamani PO;Umeyor CE;Uronnachi EM;Momoh MA;Akpa PA;Ozioko AC
通讯作者：
Ozioko AC
接枝 PEG 链构象对白蛋白和溶菌酶吸附的影响：使用 QCM-D 和 DPI 的联合研究
影响因子：
5.8
作者：
Jin, Jing;Han, Yuanyuan;Liang, Haojun
通讯作者：
Liang, Haojun
DOI：
10.2147/ijwh.s46247
发表时间：
2014
期刊：
International journal of women's health
影响因子：
--
作者：
Banerjee R;Kamrava M
通讯作者：
Kamrava M
DOI：
10.1002/adma.201404498
发表时间：
2015-02-11
期刊：
Advanced materials (Deerfield Beach, Fla.)
影响因子：
--
作者：
Jiang T;Sun W;Zhu Q;Burns NA;Khan SA;Mo R;Gu Z
通讯作者：
Gu Z
影响因子：
2
作者：
Ibrahim, Shaimaa;Tagami, Tatsuaki;Ozeki, Tetsuya
通讯作者：
Ozeki, Tetsuya