Background: Paclitaxel (PTX) is a widely used anti-cancer drug for treating various types of solid malignant tumors including breast, ovarian and lung cancers. However, PTX has a low therapeutic response and is linked with acquired resistance, as well as a high incidence of adverse events, such as allergic reactions, neurotoxicity and myelosuppression. The situation is compounded when its complex chemical structure contributes towards hydrophobicity, shortening its circulation time in blood, causing off-target effects and limiting its therapeutic activity against cancer cells. Formulating a smart nano-carrier may overcome the solubility and toxicity issues of the drug and enable its more selective delivery to the cancerous cells. Among the nano-carriers, natural polymers are of great importance due to their excellent biodegradability, non-toxicity and good accessibility. The aim of the present research is to develop self-assembled sodium caseinate nanomicelles (NaCNs) with PTX loaded into the hydrophobic core of NaCNs for effective uptake of the drug in cancer cells and its subsequent intracellular release. Methods: The PTX-loaded micelle was characterized with high-performance liquid chromatography (HPLC), Fourier Transform Infrared Spectra (FTIR), High Resolution-Transmission Electron Microscope (HR-TEM), Field Emission Scanning Electron Microscope (FESEM) and Energy Dispersive X-Ray (EDX). Following treatment with PTX-loaded NaCNs, cell viability, cellular uptake and morphological changes were analyzed using MCF-7 and MDA-MB 231 human breast cancer cell lines. Results: We found that PTX-loaded NaCNs efficiently released PTX in an acidic tumor environment, while showing an enhanced cytotoxicity, cellular uptake and in-vivo anti-tumor efficacy in a mouse model of breast cancer when compared to free drug and blank micelles. Additionally, the nanomicelles also presented improved colloidal stability for three months at 4 °C and −20 °C and when placed at a temperature of 37 °C. Conclusions: We conclude that the newly developed NaCNs is a promising carrier of PTX to enhance tumor accumulation of the drug while addressing its toxicity issues as well.

中文翻译：

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纳米结构和自组装酪蛋白胶束对紫杉醇对乳腺癌细胞增强细胞毒作用的优化与配方

背景：紫杉醇（PTX）是一种广泛使用的抗癌药物，用于治疗各种类型的实体恶性肿瘤，包括乳腺癌，卵巢癌和肺癌。然而，PTX具有较低的治疗反应，并且与获得性耐药性相关，以及诸如过敏反应，神经毒性和骨髓抑制等不良事件的发生率很高。当其复杂的化学结构导致疏水性，缩短其在血液中的循环时间，引起脱靶效应并限制其对癌细胞的治疗活性时，情况就更加复杂了。配制智能纳米载体可以克服药物的溶解性和毒性问题，并使其更选择性地递送至癌细胞。在纳米载体中，天然聚合物由于其出色的生物降解性而非常重要，无毒且易于获取。本研究的目的是开发自组装酪蛋白酸钠纳米胶束（NaCNs），其中PTX加载到NaCNs的疏水核中，以在癌细胞中有效吸收该药物并随后在细胞内释放。方法：采用高效液相色谱（HPLC），傅立叶变换红外光谱（FTIR），高分辨率透射电子显微镜（HR-TEM），场发射扫描电子显微镜（FESEM）和能量色散对负载PTX的胶束进行表征。 X射线（EDX）。用载有PTX的NaCN处理后，使用MCF-7和MDA-MB 231人乳腺癌细胞系分析细胞活力，细胞摄取和形态变化。结果：我们发现载有PTX的NaCN在酸性肿瘤环境中有效释放了PTX，与游离药物和空白胶束相比，在乳腺癌小鼠模型中显示出增强的细胞毒性，细胞摄取和体内抗肿瘤功效。此外，纳米胶束在4°C和-20°C以及放置在37°C的温度下，三个月的胶体稳定性也得到了改善。结论：我们得出结论，新开发的NaCNs是有希望的PTX载体，可增强药物的肿瘤积累，同时也解决其毒性问题。