Triptolide and celastrol loaded silk fibroin nanoparticles show synergistic effect against human pancreatic cancer cells.
Triptolide and celastrol loaded silk fibroin nanoparticles show synergistic effect against human pancreatic cancer cells.
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DOI：
10.1039/c7nr03016a
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发表时间：
2017-08-17
期刊：
影响因子：
6.7
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Ding B;Wahid MA;Wang Z;Xie C;Thakkar A;Prabhu S;Wang J
胰腺癌是一种致命的疾病，5年存活率只有5%。尽管有多种治疗方法可供选择，但预后仍然极差。因此，迫切需要结合药物的新的治疗策略来对抗这种致命的疾病。雷公藤多苷(TPL)和雷公藤红素(CL)是雷公藤中的两个主要中药成分，具有广泛的生物活性，包括抗癌活性。丝素蛋白是一种天然存在的蛋白质，具有多种独特的性质，是一种理想的载体材料。在本研究中，我们用改进的去溶法制备了负载TPL和CL的丝素纳米粒(TPL-SFNPs和CL-SFNPs)，并评价了它们对人胰腺癌细胞的协同作用。对两种SFNPs的粒度和Zeta电势进行了表征。用高效液相色谱法测定包封率、载药量和药物释放曲线。以MIA、PACA-2和PANC-1细胞为研究对象，研究了SFNPs的细胞毒性和协同作用。结果表明，TPL-SFNPs和CL-SFNPs的平均粒径分别为166.4±4.6 nm和170.4±2.3 nm，平均Zeta电位分别为−27.2±2.0 mV和−25.5±2.57 mV。TPL-SFNPs和CL-SFNPs的载药量分别为57.0±4.7μg/mg和63.5±3.8μg/mg，包封率分别为81.8±2.8%和87.0±5.1%。药物释放研究表明，SFNPs在pH 4.5(溶酶体pH)时有快速释放，在pH 7.4(血浆pH)时有延迟释放。TPL-SFNPs(IC503.80和4.75 nM)和CL-SFNPs(IC500.38和0.64μM)对MIA Paca-2和PANC-1细胞的杀伤作用是游离TPL(IC5011.25和11.58 nM)和CL(IC500.84和1.23μM)的2~3倍。此外，与TPL-SFNPs或CL-SFNPs单独作用相比，TPL-SFNPs和CL-SFNPs联合处理显著增加了对同一细胞的生长抑制。用Compusyn软件计算，几乎所有的联合指数(CI)值都为-lt；1，表明TPL-SFNPs与CL-SFNPs的联合抑制作用是协同的，而不是相加的，进一步表明这种新的组合可能为胰腺癌的治疗提供潜在的治疗方法。雷公藤甲素和雷公藤红素复合丝素纳米粒体外协同抗胰腺癌作用
Pancreatic cancer is a lethal disease with a dreadful 5-year survival rate of only 5%. In spite of several treatment options, the prognosis still remains extremely poor. Therefore, novel therapy strategies with combinations of drugs are urgently required to combat this fatal disease. Tripto-lide (TPL) and celastrol (CL), two main compounds in traditional Chinese medicine isolated from Thunder God Vine, have a broad range of bioactivities including anticancer activity. Silk fibroin (SF), a naturally occurring protein with several unique properties, is an ideal carrier mate-rial. In this study, we prepared TPL and CL loaded silk fibroin nanoparticles (TPL-SFNPs and CL-SFNPs) by a modified desolvation method and evaluated their synergistic effects against human pancreatic cancer cells. Both SFNPs were characterized for particle size and zeta poten-tial. The entrapment efficiency, drug loading, and drug release profiles were evaluated by HPLC. The cytotoxicity and synergistic effect of SFNPs were investigated in MIA PaCa-2 and PANC-1 human pancreatic cells. The results showed that the particle sizes of TPL-SFNPs and CL-SFNPs were 166.4 ± 4.6 nm and 170.4 ± 2.3 nm, with a mean zeta potential −27.2 ± 2.0 mV and −25.5 ± 2.57 mV, respectively. TPL-SFNPs and CL-SFNPs have a drug loading of 57.0 ± 4.7 μg/mg and 63.5 ± 3.8 μg/mg along with an encapsulation efficiency of 81.8 ± 2.8% and 87.0 ± 5.1%, respectively. Drug release studies revealed that a rapid release of the drugs from SFNPs was observed at pH 4.5 (lysosomal pH) and a delayed release was observed at pH 7.4 (plasma pH). TPL-SFNPs (IC50 3.80 and 4.75 nM) and CL-SFNPs (IC50 0.38 and 0.64 μM) were 2–3 fold more potent against MIA PaCa-2 and PANC-1 cells than free TPL (IC50 11.25 and 11.58 nM) and CL (IC50 0.84 and 1.23 μM). Furthermore, co-treatment with TPL-SFNPs and CL-SFNPs increased the growth inhibition of the same cells significantly in comparison with TPL-SFNPs or CL-SFNPs alone. Almost all combination index (CI) values, calculated using the Compusyn software, were < 1, suggesting that the growth inhibition effect of TPL-SFNPs in combination with CL-SFNPs was synergistic rather than additive, further suggesting that this novel combination may offer a potential treatment for pancreatic cancer. Novel combination of triptolide and celastrol loaded silk fibroin nanoparticles show synergistic anti-pancreatic cancer effect in vitro
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影响因子：
10.8
作者：
Dobrovoiskaia, Marina A.;Clogston, Jeffrey D.;Neun, Barry W.;Hall, Jennifer B.;Patri, Anil K.;McNeil, Scott E.
通讯作者：
McNeil, Scott E.
DOI：
10.3390/molecules16065283
发表时间：
2011-06-23
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Liu Z;Ma L;Zhou GB
通讯作者：
Zhou GB
影响因子：
8
作者：
Fröhlich E
通讯作者：
Fröhlich E
影响因子：
3.8
作者：
Choi, Jonghoon;Reipa, Vytas;Malinauskas, Richard A.
通讯作者：
Malinauskas, Richard A.
影响因子：
64.8
作者：
Jin, HJ;Kaplan, DL
通讯作者：
Kaplan, DL