Curcumin-encapsulating Nanogels as an Effective Anticancer Formulation for Intracellular Uptake.
Curcumin-encapsulating Nanogels as an Effective Anticancer Formulation for Intracellular Uptake.
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DOI：
10.4255/mcpharmacol.15.04
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Ahmed MM
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文献类型：
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作者：
Reeves A;Vinogradov SV;Morrissey P;Chernin M;Ahmed MM
纳米级药物递送系统代表了一种有吸引力的策略，以提高抗癌药物的疗效和安全性。在这项工作中，我们描述了姜黄素的纳米制剂，姜黄素是一种最有效的天然抗癌化合物，能够杀死癌细胞，同时保留正常组织。由于姜黄素是一种天然的疏水性多酚，它具有低的水溶性和生物利用度，这对其治疗功效具有挑战性。我们开发并评估了一种新的胶体纳米凝胶载体用于包封姜黄素，以增加其溶解度和细胞毒性。设计了纳米凝胶NG 127中的两亲性泊洛沙姆-阳离子网络以有效地包封姜黄素。得到了姜黄素含量为20-25%、粒径约为100 nm的均匀药物复合物。150 nm。使用ImageStream多光谱成像流式细胞术，我们证明了姜黄素纳米凝胶制剂（C-NG）很容易内化到MDA-231乳腺癌细胞中。使用实时细胞生长电子传感测定来测量各种乳腺癌细胞对C-NG处理的增殖反应。我们的结果表明，C-NG制剂在抑制生长方面的有效性提高了70-85%，浓度低于游离姜黄素的IC 50。这也通过改良吖啶橙子/溴化乙锭染色和荧光显微镜在形态学上证实。重要的是，单独的纳米载体NG 127几乎没有显示出细胞毒性。我们的结论是，纳米凝胶载体提供了一种创新的方式来封装姜黄素，并获得比单独姜黄素更有效的抗癌治疗药物，具有特异性肿瘤靶向的潜力，例如使用针对乳腺癌细胞特异性表面受体的抗体。
Nanoscale drug delivery systems represent an attractive strategy to improve both the efficacy and safety of anticancer drugs. In this work, we describe nanoformulation of curcumin, a most potent natural anticancer compound capable of killing cancer cells while sparing the normal tissues. Since curcumin is a natural hydrophobic polyphenol, it has a low aqueous solubility and bioavailability, which are challenging to its therapeutic efficacy. We developed and evaluated a novel colloidal nanogel carrier for encapsulation of curcumin to increase its solubility and cytotoxicity. Amphiphilic Poloxamer-cationic network in the nanogel NG127 was designed to efficiently encapsulate curcumin. Homogenous drug complexes were obtained with 20–25% content of curcumin and the particle size of ca. 150 nm. Using ImageStream multispectral imaging flow cytometry, we demonstrated that the curcumin-nanogel formulation (C-NG) was readily internalized into MDA-231 breast cancer cells. A real-time cell growth electronic sensing assay was used to measure proliferation responses of various breast cancer cells to C-NG treatments. Our results indicated that the C-NG formulation was 70–85% more effective in inhibiting growth, at concentrations lower than IC50 of free curcumin. This was also confirmed morphologically by modified acridine orange/ethidium bromide staining and fluorescent microscopy. Importantly, nanocarrier NG127 alone displayed practically no cytotoxicity. We conclude that nanogel carriers offer an innovative way to encapsulate curcumin and to obtain more effective anticancer therapeutics than curcumin alone with a potential to specific tumor targeting, such as using antibodies against surface receptors specific to breast cancer cells.