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生物源头孢噻肟偶联-银纳米粒子的纳米制剂化用于增强针对多药耐药菌的抗菌功效及抗癌研究。

Nanoformulation of Biogenic Cefotaxime-Conjugated-Silver Nanoparticles for Enhanced Antibacterial Efficacy Against Multidrug-Resistant Bacteria and Anticancer Studies.

机构信息

Division of Microbiology, Department of Biology, Faculty of Science, Taif University, Taif 21974, Saudi Arabia.

Yousef Abdullatif Jameel Chair of Prophetic Medicine Application, King Abdulaziz University, Jeddah, Saudi Arabia.

出版信息

Int J Nanomedicine. 2020 Mar 18;15:1889-1901. doi: 10.2147/IJN.S236182. eCollection 2020.

DOI:10.2147/IJN.S236182
PMID:32256066
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7090159/
Abstract

OBJECTIVES: Due to the expanded bacterial genetic tolerance to antibiotics through different mechanisms, infectious diseases of MDR bacteria are difficult for treatment. Consequently, we synthesized drug conjugated nanoparticles to dissolve this problem. Moreover, the present study aims to display the cell death status treated with cefotaxime-CS-AgNPs and also, apoptosis pathways of human RPE-1 normal cells and human MCF-7 breast cancer cells. METHODS: Here, we demonstrate the possibility to synthesize AgNPs and conjugate them with cefotaxime to survey the probability of cefotaxime-CS-AgNPs as an antimicrobial agent against cefotaxime-resistant strains and MRSA. RESULTS: TEM showed the size of AgNPs, CS-AgNPs and cefotaxime-CS-AgNPs ranged from 7.42 to 18.3 nm, 8.05-23.89 nm and 8.48-25.3 nm, respectively, with a spherical shape. The cefotaxime-CS-AgNPs enhanced the high antimicrobial properties compared to AgNPs or pure antibiotic. The MIC of Cefotaxime-CS-AgNPs ranged from 3 µg/mL to 8 µg/mL against tested and MRSA bacteria. Consequently, the highest reduction in the MIC of cefotaxime-CS-AgNPs was noted against tested strains ranging from 22% to 96%. Comparing cefotaime-CS-AgNPs to AgNPs we showed that cefotaime-CS-AgNPs have no cytotoxic effect on normal cells at even 12 µg/mL for 24 hrs. The IC50 for the AgNPs and cefotaxime-CS-AgNPs was 12 µg/mL for human RPE-1 normal cells and human MCF-7 breast cancer cell lines. The pro-apoptotic genes p53, p21, and Bax of cancer cell lines significantly upregulated followed by downregulated by anti-apoptotic gene Bcl-2 after 48 hrs at 24 µg/mL, and this concentration represents the most effective dose. CONCLUSION: Results enhanced the conjugating utility in old unresponsive cefotaxime to AgNPs to restore its efficiency against previous strains and demonstrated potential therapeutic applications of cefotaxime-CS-AgNPs. Moreover, this research gives remarkable insights for designing nanoscale delivery and curative systems that have a pronounced cytotoxic activity on cancer cells and are safe to normal cells.

摘要

目的：由于 MDR 细菌通过不同机制对抗生素的遗传耐受性扩大，因此感染性疾病难以治疗。因此，我们合成了药物偶联纳米颗粒来解决这个问题。此外，本研究旨在展示用头孢噻肟-CS-AgNPs 处理后的细胞死亡状态，以及人 RPE-1 正常细胞和人 MCF-7 乳腺癌细胞的细胞凋亡途径。

方法：在这里，我们展示了合成 AgNPs 并将其与头孢噻肟偶联以调查头孢噻肟-CS-AgNPs 作为抗头孢噻肟耐药菌株和耐甲氧西林金黄色葡萄球菌 (MRSA) 的抗菌剂的可能性。

结果：TEM 显示 AgNPs、CS-AgNPs 和头孢噻肟-CS-AgNPs 的大小分别为 7.42-18.3nm、8.05-23.89nm 和 8.48-25.3nm，呈球形。与 AgNPs 或纯抗生素相比，头孢噻肟-CS-AgNPs 增强了高抗菌性能。头孢噻肟-CS-AgNPs 的 MIC 范围为 3μg/mL 至 8μg/mL，针对测试和 MRSA 细菌。因此，头孢噻肟-CS-AgNPs 对测试菌株的 MIC 降低幅度最高为 22%至 96%。与头孢噻肟-CS-AgNPs 相比，我们表明头孢噻肟-CS-AgNPs 甚至在 12μg/mL 下孵育 24 小时对正常细胞也没有细胞毒性作用。AgNPs 和头孢噻肟-CS-AgNPs 的 IC50 分别为 12μg/mL，用于人 RPE-1 正常细胞和人 MCF-7 乳腺癌细胞系。在 24μg/mL 时，癌细胞系中的促凋亡基因 p53、p21 和 Bax 显著上调，而抗凋亡基因 Bcl-2 下调，该浓度代表最有效剂量。

结论：结果增强了将旧的无反应性头孢噻肟与 AgNPs 偶联的用途，以恢复其对以前菌株的效率，并展示了头孢噻肟-CS-AgNPs 的潜在治疗应用。此外，这项研究为设计纳米级递药和治疗系统提供了重要的见解，这些系统对癌细胞具有明显的细胞毒性活性，对正常细胞是安全的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b5c/7090159/c653a89175e3/IJN-15-1889-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b5c/7090159/7e426feaf280/IJN-15-1889-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b5c/7090159/fcb13e924fb9/IJN-15-1889-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b5c/7090159/ccde7130e4ac/IJN-15-1889-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b5c/7090159/3ffa1431bbfe/IJN-15-1889-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b5c/7090159/c653a89175e3/IJN-15-1889-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b5c/7090159/7e426feaf280/IJN-15-1889-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b5c/7090159/fcb13e924fb9/IJN-15-1889-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b5c/7090159/ccde7130e4ac/IJN-15-1889-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b5c/7090159/3ffa1431bbfe/IJN-15-1889-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b5c/7090159/c653a89175e3/IJN-15-1889-g0005.jpg

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本文引用的文献

[1]
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[2]
Antibacterial evaluation of silver nanoparticles synthesized from lychee peel: individual versus antibiotic conjugated effects.

World J Microbiol Biotechnol. 2018-7-14

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