Tannic acid-inspired paclitaxel nanoparticles for enhanced anticancer effects in breast cancer cells.
Tannic acid-inspired paclitaxel nanoparticles for enhanced anticancer effects in breast cancer cells.
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DOI：
10.1016/j.jcis.2018.09.072
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发表时间：
2019-02-01
影响因子：
9.9
通讯作者：
Yallapu MM
中科院分区：
文献类型：
--
作者：
Chowdhury P;Nagesh PKB;Hatami E;Wagh S;Dan N;Tripathi MK;Khan S;Hafeez BB;Meibohm B;Chauhan SC;Jaggi M;Yallapu MM
紫杉醇（PTX）是治疗乳腺癌、卵巢癌、胰腺癌和非小细胞肺癌的金标准化疗药物。然而，在临床使用中，PTX可能具有不良副作用或药效学参数不足，限制了其使用。纳米技术通常用于减少有效治疗所需的治疗剂量，同时也最大限度地减少化疗药物的全身副作用。然而，没有紫杉醇的纳米制剂具有内置的化学增敏基序。为了实现这一目标，我们筛选了11种药用辅料，以使用自组装方法开发替代紫杉醇纳米制剂。基于筛选结果，我们观察到单宁酸具有生产紫杉醇纳米制剂的独特性质，即，单宁酸-紫杉醇（TAP）。这种稳定的TAP纳米制剂，称为TAP纳米颗粒（TAP NPs），显示出102.22±14.05 nm的球形形状和−8.85±0.44 mV的负zeta电位。通过傅里叶变换红外（FTIR）光谱、热重分析仪（TGA）扫描和X射线衍射（XRD）证实了TAP NP中PTX的存在。PTX在TAP NP中的包封效率测定为> 96.49± 0.43%。乳腺癌细胞（MDA-MB-231）上的普通药物PTX的细胞内药物摄取显示从2-6小时或多或少恒定的药物浓度，表明药物通过P-gp转运蛋白流出，超过TAP NP，其中如通过液相色谱-串联质谱（LC-MS/MS）分析的，PTX摄取在6小时内超过95.52 ± 11.01%。各种生物测定，如增殖、克隆形成、侵袭和迁移，证实了TAP NP在所有测试浓度下优于普通PTX的上级抗癌作用。P-gp表达罗丹明-123（RH 123）、β-微管蛋白稳定化、蛋白质印迹和微阵列分析进一步证实了TAP NP的改善的治疗潜力。这些结果表明，TAP纳米制剂为开发在乳腺癌治疗中提供显著增强效果的治疗性纳米制剂提供了重要参考。
Paclitaxel (PTX) is a gold standard chemotherapeutic agent for breast, ovarian, pancreatic and non-small cell lung carcinoma. However, in clinical use PTX can have adverse side effects or inadequate pharmacodynamic parameters, limiting its use. Nanotechnology is often employed to reduce the therapeutic dosage required for effective therapy, while also minimizing the systemic side effects of chemotherapy drugs. However, there is no nano formulation of paclitaxel with chemosensitization motifs built in. With this objective, we screened eleven pharmaceutical excipients to develop an alternative paclitaxel nanoformulation using a self-assembly method. Based on the screening results, we observed tannic acid possesses unique properties to produce a paclitaxel nanoformulation, i.e., tannic acid-paclitaxel (TAP). This stable TAP nanoformulation, referred to as TAP nanoparticles (TAP NPs), showed a spherical shape of 102.22±14.05 nm and negative zeta potential of −8.85±0.44 mV. The presence of PTX in TAP NPs was confirmed by Fourier Transform Infrared (FTIR) spectra, thermogravimetric analyzer (TGA) scans, and X-ray diffraction (XRD). Encapsulation efficiency of PTX in TAP NPs was determined to be > 96.49±0.43 %. Intracellular drug uptake of plain drug PTX on breast cancer cells (MDA-MB-231) shows more or less constant drug concentration from 2–6 hours, suggesting drug efflux by the P-gp transporters, over TAP NPs, in which PTX uptake was more than 95.52+11.01% in 6 hours, as analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Various biological assays such as proliferation, clonogenic formation, invasion, and migration confirm superior anticancer effects of TAP NPs over plain PTX at all tested concentrations. P-gp expression Rhodamine-123 (RH123), beta-tubulin stabilization, Western blot, and microarray analysis further confirm the improved therapeutic potential of TAP NPs. These results suggest that the TAP nanoformulation provides an important reference for developing a therapeutic nanoformulation affording pronounced, enhanced effects in breast cancer therapy.
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DOI：
10.1088/2043-6262/7/2/025001
发表时间：
2016-06-01
影响因子：
2.1
作者：
Hoai Nam Nguyen;Phuong Thu Ha;My Nhung Hoang Thi
通讯作者：
My Nhung Hoang Thi
影响因子：
2.8
作者：
Shen M;Chan TH;Dou QP
通讯作者：
Dou QP
影响因子：
14.5
作者：
Chowdhury, Pallabita;Nagesh, Prashanth K. B.;Yallapu, Murali M.
通讯作者：
Yallapu, Murali M.
影响因子：
4.8
作者：
McGarrigle, D;Shan, DD;Huang, XY
通讯作者：
Huang, XY
影响因子：
3.8
作者：
Jackson, John K.;Letchford, Kevin
通讯作者：
Letchford, Kevin