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负载化学增敏剂的近红外响应性纳米结构脂质载体:一种用于耐药性乳腺癌协同治疗的工具

Chemosensitizer Loaded NIR-Responsive Nanostructured Lipid Carriers: A Tool for Drug-Resistant Breast Cancer Synergistic Therapy.

作者信息

Okuyucu Cigdemnaz Ersoz, Kalaycioglu Gokce Dicle, Ozden Ayse Kevser, Aydogan Nihal

机构信息

Department of Chemical Engineering, Hacettepe University, Beytepe, Ankara 06800, Turkey.

Faculty of Medicine, Medical Biology Department, Lokman Hekim University, Ankara 06530, Turkey.

出版信息

ACS Appl Bio Mater. 2025 Mar 17;8(3):2167-2181. doi: 10.1021/acsabm.4c01675. Epub 2025 Feb 18.

Abstract

Although numerous technical advances have been made in cancer treatment, chemotherapy is still a viable treatment option. However, it is more effective when used in combination with photothermal therapy for resistant breast cancer cells. This study introduces a smart drug delivery system, (DOX-OA+VERA+AuNRs)@NLC, which is designed for dual chemo/photothermal therapy of multiple-drug-resistant breast cancer. Type-III nanostructured lipid carriers (NLCs) were used as drug delivery systems, where nano-in-nano structures offer several advantages. Doxorubicin (DOX) was used as the antitumor agent by ion-pairing it with oleic acid (OA) to increase the DOX loading capacity, as well as to reduce the burst release of the drug. Verapamil (VERA), which was used as a chemosensitizer to overcome the multiple-drug resistance, was co-loaded with DOX-OA. Gold nanorods (AuNRs) were exploited as the photothermal therapy agent in photothermal therapy (PTT) application, which would have a synergistic relation with chemotherapy. The release of DOX-OA and VERA from NLCs was studied by triggering with NIR laser irradiation. Thus, an all-in-one drug delivery system was designed to release the active pharmaceutical ingredients (APIs) at higher concentrations in the desired region and provide both chemo/PTT. Besides, the application of a folic acid-chitosan (FA-CS) coating to NLCs has facilitated the development of systems capable of targeting and specifically releasing their cargo within cancerous tissues while preserving their surrounding environment.

摘要

尽管癌症治疗已取得众多技术进步,但化疗仍是一种可行的治疗选择。然而,将其与光热疗法联合用于耐药乳腺癌细胞时效果更佳。本研究引入了一种智能药物递送系统,即(DOX-OA+VERA+AuNRs)@NLC,其设计用于多药耐药乳腺癌的双重化疗/光热治疗。III型纳米结构脂质载体(NLCs)被用作药物递送系统,其中纳米包纳米结构具有多种优势。阿霉素(DOX)通过与油酸(OA)离子配对用作抗肿瘤剂,以提高DOX的负载能力,并减少药物的突释。维拉帕米(VERA)用作化学增敏剂以克服多药耐药性,与DOX-OA共同负载。金纳米棒(AuNRs)在光热治疗(PTT)应用中用作光热治疗剂,其与化疗具有协同关系。通过近红外激光照射触发,研究了DOX-OA和VERA从NLCs中的释放情况。因此,设计了一种一体化药物递送系统,以在所需区域以更高浓度释放活性药物成分(APIs),并提供化疗/PTT。此外,在NLCs上应用叶酸-壳聚糖(FA-CS)涂层有助于开发能够在癌组织内靶向并特异性释放其载药同时保护周围环境的系统。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b8/11921034/f042df01967c/mt4c01675_0001.jpg

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