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多功能壳聚糖双金属纳米载体递送 5-氟尿嘧啶,增强胰腺癌和三阴性乳腺癌的治疗效果。

Multifunctional chitosan-bimetallic nanocarrier deliver 5-fluorouracil for enhanced treatment of pancreatic and triple-negative breast cancer.

机构信息

Department of Bio-Health Convergence, Kangwon National University, Chuncheon 200-701, Republic of Korea.

Department of Applied Chemistry, Kumoh National Institute of Technology, Gumi, Gyeongbuk 730-701, Republic of Korea.

出版信息

Int J Biol Macromol. 2024 Feb;259(Pt 1):129165. doi: 10.1016/j.ijbiomac.2023.129165. Epub 2023 Dec 30.


DOI:10.1016/j.ijbiomac.2023.129165
PMID:38163501
Abstract

This work aimed to prepare multifunctional aptamer-conjugated, photothermally responsive 5-fluorouracil (5fu)-loaded chitosan-bimetallic (Au/Pd) nanoparticles (APT-CS-5fu-Au/Pd NPs) for improved cytotoxicity in two cancer cell lines (PANC-1 and MDA-MD 231). The CS-5fu-Au/Pd NPs were polydispersed with a size of 34.43 ± 1.59 nm. FTIR analysis indicated the presence of CS, 5fu in CS-5fu-Au/Pd NPs. The 2 theta degrees in CS-5fu-Au/Pd NPs accounted for CS and Au/Pd. Additionally, AGE revealed the conjugation of APT in CS-5fu-Au/Pd NPs. The APT-CS-5fu-Au/Pd NPs (180 μg/mL) with NIR treatment increased the temperature to >50 °C. The optimized 5fu input was 0.075 % in CS-5fu-Au/Pd NPs, exhibiting a hydrodynamic size of 112.96 ± 17.23 nm, DEE of 64.2 ± 3.77 %, and DLE of 11.1 ± 0.65 %. A higher level of 5fu release (69.8 ± 2.78 %) was observed under pH 5.4 at 74 h. In conclusion, NIR-APT-CS-5fu-Au/Pd NPs did not cause toxicity to RBC and Egg CAM, but increased cytotoxicity in MDA-MB 231 and PANC-1 cells by triggering oxidative stress-mediated cell death.

摘要

这项工作旨在制备多功能适体偶联的、光热响应的 5-氟尿嘧啶(5fu)负载壳聚糖双金属(Au/Pd)纳米粒子(APT-CS-5fu-Au/Pd NPs),以提高两种癌细胞系(PANC-1 和 MDA-MD 231)的细胞毒性。CS-5fu-Au/Pd NPs 呈多分散性,粒径为 34.43±1.59nm。傅里叶变换红外(FTIR)分析表明 CS-5fu-Au/Pd NPs 中存在 CS 和 5fu。CS-5fu-Au/Pd NPs 的 2 theta 度代表 CS 和 Au/Pd。此外,AGE 显示 APT 与 CS-5fu-Au/Pd NPs 的偶联。具有 NIR 处理的 APT-CS-5fu-Au/Pd NPs(180μg/mL)可将温度升高至>50°C。CS-5fu-Au/Pd NPs 中最佳 5fu 输入为 0.075%,表现出 112.96±17.23nm 的水动力粒径、64.2±3.77%的 DEE 和 11.1±0.65%的 DLE。在 74 小时时,在 pH 5.4 下观察到 69.8±2.78%的更高水平的 5fu 释放。总之,NIR-APT-CS-5fu-Au/Pd NPs 不会引起 RBC 和 Egg CAM 的毒性,但通过引发氧化应激介导的细胞死亡,增加了 MDA-MB 231 和 PANC-1 细胞的细胞毒性。

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