Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Germany; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Germany; Department of Pharmacy, The University of Lahore, Lahore, Pakistan.
Biomater Adv. 2022 Mar;134:112543. doi: 10.1016/j.msec.2021.112543. Epub 2021 Nov 12.
Parietin (PTN) is an anthraquinone with promising efficacy in the inhibition of cancer cell proliferation and tumor growth. Due to its hydrophobicity, PTN is sparingly soluble under physiological conditions and has a low bioavailability. Hence, we presented PTN in liposomes to overcome these drawbacks. The prepared liposomes were characterized and their stability was also assessed in serum. Singlet oxygen quantum yield of PTN loaded liposomes was indirectly quantified using uric acid. The intracellular uptake of liposomes was studied by CLSM which indicated the perinuclear localization of PTN liposomes. Cellular viability assay and live/dead staining demonstrated both light and dose-dependent phototoxicity of PTN on the human breast cancer cell line. The mechanism of cellular uptake was investigated using different pathway inhibitors and the results showed that clathrin-mediated endocytosis is predominant. The colocalization experiment indicated that PTN is localized in both mitochondria and lysosomes. These findings together with flow cytometry analysis elucidated that apoptosis is the main mechanism underlying cell death post-PDT. Finally, the antiangiogenic effect of PTN liposomes was further evaluated in the chorioallantoic membrane (CAM) model and the results indicated that PDT induced vascular response was confined to the irradiated area leaving the non-irradiated unscathed.
帕里丁（PTN）是一种蒽醌类化合物，具有抑制癌细胞增殖和肿瘤生长的良好效果。由于其疏水性，PTN 在生理条件下溶解度较低，生物利用度低。因此，我们将 PTN 包封于脂质体中以克服这些缺点。对制备的脂质体进行了表征，并在血清中评估了其稳定性。使用尿酸间接定量载有 PTN 的脂质体的单线态氧量子产率。通过 CLSM 研究了脂质体的细胞内摄取，结果表明 PTN 脂质体定位于核周。细胞活力测定和死活染色表明，PTN 对人乳腺癌细胞系具有光和剂量依赖性的光毒性。使用不同途径抑制剂研究了细胞摄取的机制，结果表明网格蛋白介导的内吞作用占主导地位。共定位实验表明，PTN 定位于线粒体和溶酶体中。这些发现与流式细胞术分析一起阐明，细胞死亡是 PDT 后细胞死亡的主要机制。最后，在鸡胚尿囊膜（CAM）模型中进一步评估了 PTN 脂质体的抗血管生成作用，结果表明 PDT 诱导的血管反应局限于照射区域，未照射区域未受影响。
