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负载氯化巴马汀的壳聚糖纳米粒用于增强型安全宫颈癌治疗的研发。

Development of palmatine chloride-loaded chitosan nanoparticles for enhanced and safe cervical cancer therapy.

作者信息

Wang Houhong, Shang Kelei, Tang Ke, Duan Zemeng, Xu Menglei, Luo Chun, Shen Yamei

机构信息

Department of General Surgery, The Affiliated First Hospital of Fuyang Normal University, China.

Department of Paediatric Surgery, The Affiliated First Hospital of Fuyang Normal University, China.

出版信息

Int J Biol Macromol. 2025 Sep;322(Pt 1):146579. doi: 10.1016/j.ijbiomac.2025.146579. Epub 2025 Aug 8.

Abstract

Cervical cancer remains a significant global health issue, highlighting the need for novel drug delivery strategies to improve the efficacy of anticancer agents against it. In this study, palmatine chloride-loaded chitosan nanoparticles (PC-CSNPs) were developed via ionic gelation as biocompatible nanocarriers for cervical cancer therapy. The physical properties of PCNPs were characterized using SEM, FTIR, XRD, and DLS, revealing a spherical morphology and average particle sizes of 55 nm (chitosan) and 58 nm (PCNPs).FTIR and XRD confirmed successful drug encapsulation and an amorphous structure of the nanoparticles. Drug loading and encapsulation efficiencies increased in a dose-dependent manner, with maximum encapsulation (80.2 %) at 40 μg and enhanced retention at acidic pH. PCNPs exhibited notable antioxidant activity, with peak efficacy at 100 μg/mL. Antimicrobial activity was most pronounced against Streptococcus pneumoniae (1.9 mm zone at 75 μg/mL concentration).In vitro anticancer studies on HeLa cells revealed strong cytotoxicity, with an IC of 26.057 ± 0.56 μg/mL. AO/EtBr dual staining, reactive oxygen species (ROS) detection, and Hoechst staining were confirmed dose-dependent apoptosis, oxidative stress, and nuclear condensation, respectively. Zebrafish assays revealed developmental abnormalities and mortality at higher concentrations, while AO and DPPP staining indicated increased apoptosis and lipid peroxidation. Overall, PCNPs demonstrated promising potential as a targeted and efficient drug delivery platform for cervical cancer therapy. However, dosage optimization remains critical to ensure their safety and effectiveness in biomedical applications.

摘要

宫颈癌仍然是一个重大的全球健康问题,这凸显了需要新的药物递送策略来提高抗癌药物对其的疗效。在本研究中,通过离子凝胶法制备了负载盐酸巴马汀的壳聚糖纳米粒(PC-CSNPs),作为用于宫颈癌治疗的生物相容性纳米载体。使用扫描电子显微镜(SEM)、傅里叶变换红外光谱(FTIR)、X射线衍射(XRD)和动态光散射(DLS)对PCNPs的物理性质进行了表征,结果显示其呈球形形态,壳聚糖的平均粒径为55nm,PCNPs的平均粒径为58nm。FTIR和XRD证实了药物的成功包封以及纳米粒的无定形结构。载药量和包封率呈剂量依赖性增加,在40μg时包封率最高(80.2%),且在酸性pH下保留率提高。PCNPs表现出显著的抗氧化活性,在100μg/mL时功效峰值最高。抗菌活性对肺炎链球菌最为显著(在75μg/mL浓度下抑菌圈为1.9mm)。对HeLa细胞的体外抗癌研究显示出强烈的细胞毒性,半数抑制浓度(IC)为26.057±0.56μg/mL。吖啶橙/溴化乙锭(AO/EtBr)双染色、活性氧(ROS)检测和Hoechst染色分别证实了剂量依赖性的细胞凋亡、氧化应激和核浓缩。斑马鱼试验显示在较高浓度下存在发育异常和死亡,而AO和二苯基膦酸(DPPP)染色表明细胞凋亡和脂质过氧化增加。总体而言,PCNPs作为宫颈癌治疗的靶向高效药物递送平台显示出有前景的潜力。然而,剂量优化对于确保其在生物医学应用中的安全性和有效性仍然至关重要。

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