维替泊芬二聚体自组装成叶酸受体靶向脂质纳米颗粒用于卵巢癌光动力治疗

IF 6.1 2区 医学 Q1 ENGINEERING, BIOMEDICAL
Carla Arnau del Valle, Payal Srivastava, Kathryn McNaughton, Huang‐Chiao Huang
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引用次数: 0

摘要

光动力疗法(PDT)是一种微创治疗方法,包括使用可光激活的药物,然后光激活病变部位,产生杀死癌细胞的活性氧。Visudyne®是一种苯并卟啉衍生物(BPD)光敏剂的脂质体制剂,已被临床批准用于眼部疾病的PDT治疗,目前正在测试用于胰腺、脑癌和其他癌症的PDT和成像。虽然Visudyne®改善了BPD的药代动力学,但它缺乏治疗选择性。为了减少PDT相关的副作用,如皮肤和肠道毒性,同时提高治疗效果,开发针对癌症的BPD纳米技术至关重要。许多癌症的特点是叶酸受体(FR)的过度表达和谷胱甘肽(GSH)的高水平。在这里,我们报道了一种可被红光激活的二聚体- BPD (dBPD)的合成,用于癌细胞的PDT和成像。自组装脂质纳米颗粒(NPs)是由dBPD聚集形成的,并与FA (FA - dBPD - NPs)进一步功能化,并通过GSH裂解二硫连接体具有药物释放能力。FA - dBPD - NPs在卵巢癌细胞中表现出高药物负荷、GSH触发的释放效应、FRs过表达细胞靶向、内质网积累和有效的PDT。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Self‐assembly of verteporfin dimers into folate receptor‐targeted lipid nanoparticles for photodynamic therapy of ovarian cancer
Photodynamic therapy (PDT) is a minimally invasive treatment that involves the administration of a light‐activatable drug followed by light activation of the lesion to produce reactive oxygen species that kill cancer cells. Visudyne®, a liposomal formulation of benzoporphyrin derivative (BPD) photosensitizer, is clinically approved for PDT of ocular diseases and is now being tested for PDT and imaging of pancreatic, brain, and other cancers. While Visudyne® improves the pharmacokinetics of BPD, it lacks treatment selectivity. To reduce PDT‐associated side effects such as skin and bowel toxicity while enhancing therapeutic outcomes, developing cancer‐targeted BPD nanotechnology is essential. Many cancers are characterized by overexpression of folate receptor (FR) and present high levels of glutathione (GSH). Here, we report the synthesis of a dimeric‐BPD (dBPD) activatable by red light for PDT and imaging of cancer cells. Self‐assembled lipid nanoparticles (NPs) are developed by the aggregation of dBPD and further functionalized with FA (FA‐dBPD‐NPs) and with drug release capability via cleavage of the disulfide linkers through GSH. The FA‐dBPD‐NPs present high drug payload, GSH‐triggered release effect, FRs overexpressing cell targeting, endoplasmic reticulum accumulation, and effective PDT in ovarian cancer cells.
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来源期刊
Bioengineering & Translational Medicine
Bioengineering & Translational Medicine Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
8.40
自引率
4.10%
发文量
150
审稿时长
12 weeks
期刊介绍: Bioengineering & Translational Medicine, an official, peer-reviewed online open-access journal of the American Institute of Chemical Engineers (AIChE) and the Society for Biological Engineering (SBE), focuses on how chemical and biological engineering approaches drive innovative technologies and solutions that impact clinical practice and commercial healthcare products.
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