关键词: Chemoresistance Nanoparticle Ovarian cancer Protoporphyrin Thioredoxin

Mesh : Humans Photosensitizing Agents / pharmacology Reactive Oxygen Species Drug Resistance, Neoplasm Photochemotherapy / methods Nanoparticles Neoplasms Cell Line, Tumor

来  源:   DOI:10.1016/j.nano.2023.102688

Abstract:
Chemoresistance is the main cause of chemotherapy failure in ovarian cancer (OC). The enhanced scavenging of reactive oxygen species (ROS) by the thioredoxin system resulted in insufficient intracellular concentrations of effective ROS, leading to chemoresistance. To induce OC cell apoptosis by enhancing intracellular ROS levels, protoporphyrin IX (PpIX) and albumin-bound PTX nanoparticles (APNP) were utilized to fabricate APNP-PpIX nanoparticles. APNP-PpIX effectively generated ROS and increased the effective ROS concentration in chemoresistant cancer cells. The in vitro and in vivo experiments confirmed the effective inhibition of APNP-PpIX on chemoresistant OC cell proliferation and tumor formation. APNP-PpIX significantly improved the effectiveness of chemotherapy and photodynamic therapy, thus providing a new approach for the clinical treatment of chemoresistant OC.
摘要:
化疗耐药是卵巢癌化疗失败的主要原因。硫氧还蛋白系统对活性氧(ROS)的增强清除导致细胞内有效ROS浓度不足,导致化学抗性。通过提高细胞内ROS水平诱导OC细胞凋亡,原卟啉IX(PpIX)和白蛋白结合的PTX纳米颗粒(APNP)用于制造APNP-PpIX纳米颗粒。APNP-PpIX有效地产生ROS并增加化学抗性癌细胞中的有效ROS浓度。体外和体内实验证实了APNP-PpIX对化学抗性OC细胞增殖和肿瘤形成的有效抑制。APNP-PpIX显著提高了化疗和光动力治疗的有效性,从而为临床治疗化疗耐药OC提供了新的途径。
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