State Key Laboratory of Genetic Engineering, Department of Pharmaceutical Sciences, School of Life Sciences, Fudan University, Shanghai 200438, China.
State Key Laboratory of Genetic Engineering, Department of Pharmaceutical Sciences, School of Life Sciences, Fudan University, Shanghai 200438, China.
Acta Biomater. 2018 Jun;73:400-411. doi: 10.1016/j.actbio.2018.04.020. Epub 2018 Apr 14.
Estrone-modified glycol chitosan nanoparticles (GCNP-ES) based on the mechanisms of ES-mediated endocytosis and intracellular pH-responsive drug release were developed for the treatment of breast cancer. GCNP-ES were prepared by grafting copolymerization of glycol chitosan with 2-(diisopropylamino)ethyl methacrylate to generate GCNP prior to ES conjugation. The particle size, zeta potential, and paclitaxel (PTX) encapsulation efficiency of GCNP-ES were characterized. In particular, GCNP-ES exhibited pH-responsive dissociation properties while maintaining stability under long-term storage and lyophilization. The drug release of PTX-loaded GCNP-ES (PTX/GNCP-ES) was modestly prolonged with considerable pH sensitivity. GCNP-ES promoted internalization in breast cancer MCF-7 cells by approximately 5-fold as compared to GCNP, and the internalized GCNP-ES was mainly localized in the endosomes of MCF-7 cells. PTX/GNCP-ES exhibited higher cytotoxicity and cell apoptosis ratio than GCNP. In mice with MCF-7 breast cancer xenograft, PTX/GCNP-ES showed higher accumulation at the tumor site, which resulted in a higher tumor inhibition ratio (81.4%) than that achieved by PTX/GCNP (69.4%) and PTX solution (48.8%). Furthermore, no histological and hematological toxicity was detected in in vivo studies of PTX/GCNP-ES. Overall, these results suggested the potential applicability of GCNP-ES as a drug delivery system for breast cancer therapy.
Most breast cancers are hormone dependent. Herein, we developed a estrone-modified glycol chitosan nanoparticles (GCNP-ES) as a drug delivery system to overcome the drawbacks of chemotherpeutic drugs, including poor water solubility and lack of specifity. GCNP-ES could provide efficient drug delivery in breast cancer cells. The study demonstrated that GCNP-ES could dissociate under mildly acidic conditions, leading to the timely payload release of the drug in target tumor cells following internalization. The conjugated estrone of the nanoparticles could significantly increase drug accumulation in the tumor site and result in enhanced therapeutic effect. Thus, the potential applicability of GCNP-ES was suggested.
基于雌酮介导的内吞作用和细胞内 pH 响应性药物释放机制，开发了雌酮修饰的乙二醇壳聚糖纳米颗粒（GCNP-ES），用于治疗乳腺癌。通过乙二醇壳聚糖与 2-（二异丙基氨基）乙基甲基丙烯酸酯的接枝共聚反应制备 GCNP-ES，生成 GCNP 后再进行 ES 偶联。对 GCNP-ES 的粒径、Zeta 电位和紫杉醇（PTX）包封效率进行了表征。特别是，GCNP-ES 表现出 pH 响应性解离特性，同时在长期储存和冻干条件下保持稳定性。负载 PTX 的 GCNP-ES（PTX/GNCP-ES）的药物释放得到适度延长，且具有相当的 pH 敏感性。与 GCNP 相比，GCNP-ES 可使乳腺癌 MCF-7 细胞的内化作用增加约 5 倍，内化的 GCNP-ES 主要定位于 MCF-7 细胞的内体中。PTX/GNCP-ES 的细胞毒性和细胞凋亡率均高于 GCNP。在 MCF-7 乳腺癌异种移植小鼠模型中，PTX/GCNP-ES 在肿瘤部位的积累更高，肿瘤抑制率（81.4%）高于 PTX/GCNP（69.4%）和 PTX 溶液（48.8%）。此外，在体内研究中未检测到 PTX/GCNP-ES 的组织学和血液学毒性。总的来说，这些结果表明 GCNP-ES 作为一种用于乳腺癌治疗的药物传递系统具有潜在的应用前景。
大多数乳腺癌是激素依赖性的。本文开发了一种雌酮修饰的乙二醇壳聚糖纳米颗粒（GCNP-ES）作为药物传递系统，以克服化疗药物的缺点，包括水溶性差和缺乏特异性。GCNP-ES 可以在乳腺癌细胞中提供有效的药物传递。研究表明，GCNP-ES 可以在酸性条件下解离，导致药物在靶肿瘤细胞内化后及时释放。纳米颗粒的共轭雌酮可以显著增加肿瘤部位的药物积累，从而增强治疗效果。因此，提示 GCNP-ES 具有潜在的应用前景。
