Evaluating a targeted Palbociclib-Trastuzumab loaded smart niosome platform for treating HER2 positive breast cancer cells

IF 5.2 2区医学 Q1 PHARMACOLOGY & PHARMACY International Journal of Pharmaceutics: X Pub Date : 2024-03-11 DOI:10.1016/j.ijpx.2024.100237

Shaghayegh Saharkhiz , Negar Nasri , Nazanin Naderi , Ghasem Dini , Saeid Shirzadi Ghalehshahi , Fateme Firoozbakht

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Abstract

In this study, we present a targeted and pH-sensitive niosomal (pHSN) formulation, incorporating quantum dot (QD)-labeled Trastuzumab (Trz) molecules for the specific delivery of Palbociclib (Pal) to cells overexpressing human epidermal growth factor receptor 2 (HER2). FTIR analyses confirmed the successful preparation of the pHSNs and their bioconjugation. The labeled Trz-conjugated Pal-pHSNs (Trz-Pal-pHSNs) exhibited a size of approximately 170 nm, displaying a spherical shape with a neutral surface charge of −1.2 mV. Pal encapsulation reached ∼86%, and the release pattern followed a two-phase pH-dependent mechanism. MTT assessments demonstrated enhanced apoptosis induction, particularly in HER2-positive cells, by Trz-Pal-pHSNs. Fluorescence imaging further validated the internalization of particles into cells. In conclusion, Trz-Pal-pHSNs emerge as a promising platform for personalized medicine in the treatment of HER2-positive breast cancer.

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评估用于治疗 HER2 阳性乳腺癌细胞的靶向 Palbociclib-Trastuzumab 负载智能 niosome 平台

在这项研究中，我们提出了一种具有靶向性和 pH 值敏感性的 niosomal（pHSN）制剂，其中加入了量子点（QD）标记的曲妥珠单抗（Trz）分子，用于将 Palbociclib（Pal）特异性地递送到过表达人表皮生长因子受体 2（HER2）的细胞中。傅立叶变换红外分析证实了 pHSNs 的成功制备及其生物共轭。标记的Trz-共轭Pal-pHSNs（Trz-Pal-pHSNs）大小约为170 nm，呈球形，表面中性电荷为-1.2 mV。Pal 的封装率达到了 ∼86%，释放模式遵循两相 pH 依赖性机制。MTT 评估表明，Trz-Pal-pHSNs 增强了细胞凋亡诱导作用，尤其是在 HER2 阳性细胞中。荧光成像进一步验证了颗粒在细胞内的内化。总之，Trz-Pal-pHSNs 是治疗 HER2 阳性乳腺癌的一种前景广阔的个性化医疗平台。

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