■乳腺癌是最常见的癌症之一,主要影响女性。在它的亚型中,雌激素受体阳性(ER+)乳腺癌尤其常见。抑制雌激素的作用对于治疗ER+乳腺癌至关重要,但目前的治疗方法往往有明显的副作用和局限性.Chyrin,一种天然类黄酮,已经显示出降低雌激素受体表达的潜力,但其水溶性差阻碍了临床应用。本研究探索了使用介孔多巴胺纳米颗粒(mPDA)来增强白杨素的递送和功效,结合光热疗法(PTT),用于乳腺癌治疗。
■合成了载有Chrysin的mPDA纳米颗粒(Chrysin@mPDA),并对其形态进行了表征,药物装载效率,稳定性,和光热特性。网络药理学用于预测Chrysin在乳腺癌中的作用机制,通过细胞实验中的基因表达分析进行了验证。在乳腺癌小鼠模型中评估了含和不含PTT的Chryin@mPDA的治疗效果,测量肿瘤体积和重量。进行免疫组织化学分析以评估肿瘤组织中的雌激素受体表达和免疫细胞浸润。
■Chrysin@mPDA纳米颗粒表现出高载药能力和优异的稳定性。光热研究证实了纳米粒子在激光照射时产生热量的能力,用激光照射显着增强酸性条件下的Chryin释放。网络药理学确定了受Chryin影响的关键靶基因,包括ESR1、BRCA1、CTNNB1和BAX,通过qPCR验证。在体内,Chrysin@mPDA和PTT的组合显着降低了肿瘤的体积和重量,雌激素受体阳性细胞减少,肿瘤组织中CD3+CD4+和CD3+CD8+T细胞浸润增加。
■该研究强调了负载Chrysin的mPDA纳米颗粒与PTT联合作为乳腺癌治疗有效策略的潜力。这种方法解决了菊素溶解度的局限性,并通过协同机制增强了其治疗功效。Chryin在调节基因表达和PTT在诱导局部热疗和免疫反应中的双重作用表明了改善乳腺癌预后和减少复发的有希望的途径。
UNASSIGNED: Breast cancer is one of the most prevalent cancers, primarily affecting women. Among its subtypes, estrogen receptor-positive (ER+) breast cancer is particularly common. Inhibiting estrogen\'s effects is crucial for treating ER+ breast cancer, but current therapies often have significant side effects and limitations.
Chrysin, a natural flavonoid, has shown potential in reducing estrogen receptor expression, but its poor water solubility hampers clinical application. This study explores the use of mesoporous dopamine nanoparticles (mPDA) to enhance the delivery and efficacy of Chrysin, combined with photothermal therapy (PTT), for breast cancer treatment.
UNASSIGNED: Chrysin-loaded mPDA nanoparticles (
Chrysin@mPDA) were synthesized and characterized for their morphology, drug-loading efficiency, stability, and photothermal properties. Network pharmacology was used to predict
Chrysin\'s mechanisms in breast cancer, which were validated through gene expression analysis in cell experiments. The therapeutic efficacy of
Chrysin@mPDA with and without PTT was evaluated in a mouse model of breast cancer, with tumor volume and weight measured. Immunohistochemical analysis was conducted to assess estrogen receptor expression and immune cell infiltration in tumor tissues.
UNASSIGNED: Chrysin@mPDA nanoparticles demonstrated a high drug-loading capacity and excellent stability. Photothermal studies confirmed the nanoparticles\' ability to generate heat upon laser exposure, significantly enhancing Chrysin release in acidic conditions with laser irradiation. Network pharmacology identified key target genes affected by
Chrysin, including ESR1, BRCA1, CTNNB1, and BAX, which were validated through qPCR. In vivo, the combination of Chrysin@mPDA and PTT significantly reduced tumor volume and weight, decreased estrogen receptor-positive cells, and increased infiltration of CD3+CD4+ and CD3+CD8+ T cells in tumor tissues.
UNASSIGNED: The study highlights the potential of Chrysin-loaded mPDA nanoparticles combined with PTT as an effective strategy for breast cancer treatment. This approach addresses the limitations of Chrysin\'s solubility and enhances its therapeutic efficacy through synergistic mechanisms. The dual action of Chrysin in modulating gene expression and PTT in inducing localized hyperthermia and immune response suggests a promising avenue for improved breast cancer prognosis and reduced recurrence.