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用于抗真菌治疗应用的载牛乳铁蛋白的等离子体磁脂质体

Bovine Lactoferrin-Loaded Plasmonic Magnetoliposomes for Antifungal Therapeutic Applications.

作者信息

Pereira Mélanie, Rodrigues Ana Rita O, Amaral Leslie, Côrte-Real Manuela, Santos-Pereira Cátia, Castanheira Elisabete M S

机构信息

Physics Centre of Minho and Porto Universities (CF-UM-UP), University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal.

LaPMET (Laboratory of Physics for Materials and Emergent Technologies), Associate Laboratory, 4710-057 Braga, Portugal.

出版信息

Pharmaceutics. 2023 Aug 19;15(8):2162. doi: 10.3390/pharmaceutics15082162.


DOI:10.3390/pharmaceutics15082162
PMID:37631376
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10458800/
Abstract

Bovine lactoferrin (bLf) is a milk-derived protein that exhibits potent broad-spectrum antifungal activity against multiple fungi. bLf is susceptible to degradation, while some of its properties depend on the tertiary structure. So, the encapsulation of bLf in stimuli-responsive therapeutic formulations provides an added value to enhance its biological activities. Plasmonic magnetoliposomes (PMLs) arise as promising nanocarriers for dual hyperthermia (magneto-photothermia) and local chemotherapy, since the combination of magnetic and gold nanoparticles (NPs) in a single nanosystem (multifunctional liposomes) enables the targeting and controlled release of loaded drugs. In this work, plasmonic magnetoliposomes (PMLs) containing manganese ferrite nanoparticles (28 nm size) and gold nanoparticles (5-7.5 nm size), functionalized with 11-mercaptoundecanoic acid or octadecanethiol, were prepared and loaded with bLf. The NPs' optical, magnetic and structural properties were measured via UV/vis/NIR absorption spectroscopy, SQUID and TEM, respectively. The Specific Absorption Rate (SAR) was calculated to assess the capabilities for magnetic and photothermal hyperthermia. Finally, the antifungal potential of bLf-loaded PMLs and their mechanism of internalization were assessed in by counting the colony forming units and using fluorescence microscopy. The results demonstrate that PMLs are mainly internalized through an energy- and temperature-dependent endocytic process, though the contribution of a diffusion component cannot be discarded. Most notably, only bLf-loaded plasmonic magnetoliposomes display cytotoxicity with an efficiency similar to free bLf, attesting their promising potential for bLf delivery in the context of antifungal therapeutic interventions.

摘要

牛乳铁蛋白(bLf)是一种源自牛奶的蛋白质,对多种真菌具有强大的广谱抗真菌活性。bLf易于降解,而其一些特性取决于三级结构。因此,将bLf封装在刺激响应性治疗制剂中可增加其生物活性。等离子体磁脂质体(PMLs)作为用于双重热疗(磁光热疗)和局部化疗的有前景的纳米载体出现,因为在单个纳米系统(多功能脂质体)中磁性和金纳米颗粒(NPs)的组合能够实现负载药物的靶向和控释。在这项工作中,制备了含有锰铁氧体纳米颗粒(尺寸为28nm)和金纳米颗粒(尺寸为5 - 7.5nm)的等离子体磁脂质体(PMLs),并用11 - 巯基十一烷酸或十八烷硫醇进行功能化,然后负载bLf。分别通过紫外/可见/近红外吸收光谱、超导量子干涉仪和透射电子显微镜测量了纳米颗粒的光学、磁性和结构性质。计算了比吸收率(SAR)以评估磁热疗和光热疗的能力。最后,通过计数菌落形成单位并使用荧光显微镜评估了负载bLf的PMLs的抗真菌潜力及其内化机制。结果表明,PMLs主要通过能量和温度依赖性的内吞过程内化,尽管不能排除扩散成分的作用。最值得注意的是,只有负载bLf的等离子体磁脂质体显示出与游离bLf相似效率的细胞毒性,证明了它们在抗真菌治疗干预中递送bLf的潜在前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5cb/10458800/1061d96e3f39/pharmaceutics-15-02162-g015.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5cb/10458800/e6a89cd9d946/pharmaceutics-15-02162-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5cb/10458800/2048d0023c69/pharmaceutics-15-02162-g011.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5cb/10458800/536749dc3891/pharmaceutics-15-02162-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5cb/10458800/a1ff5fb41c38/pharmaceutics-15-02162-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5cb/10458800/9cfc16b029dc/pharmaceutics-15-02162-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5cb/10458800/504f7b7161e0/pharmaceutics-15-02162-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5cb/10458800/e6a89cd9d946/pharmaceutics-15-02162-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5cb/10458800/2048d0023c69/pharmaceutics-15-02162-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5cb/10458800/c045f334b37c/pharmaceutics-15-02162-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5cb/10458800/7fa0db71675d/pharmaceutics-15-02162-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5cb/10458800/268bf6a861ca/pharmaceutics-15-02162-g014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5cb/10458800/1061d96e3f39/pharmaceutics-15-02162-g015.jpg

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引用本文的文献

[1]
Lactoferrin as a Versatile Agent in Nanoparticle Applications: From Therapeutics to Agriculture.

Nanomaterials (Basel). 2024-12-16

[2]
Elastic Liposomes Containing Calcium/Magnesium Ferrite Nanoparticles Coupled with Gold Nanorods for Application in Photothermal Therapy.

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本文引用的文献

[1]
Development of pH-Sensitive Magnetoliposomes Containing Shape Anisotropic Nanoparticles for Potential Application in Combined Cancer Therapy.

Nanomaterials (Basel). 2023-3-15

[2]
Can Lactoferrin, a Natural Mammalian Milk Protein, Assist in the Battle against COVID-19?

Nutrients. 2022-12-10

[3]
Lactoferrin perturbs intracellular trafficking, disrupts cholesterol-rich lipid rafts and inhibits glycolysis of highly metastatic cancer cells harbouring plasmalemmal V-ATPase.

Int J Biol Macromol. 2022-11-1

[4]
Lactoferrin for iron-deficiency anemia in children with inflammatory bowel disease: a clinical trial.

Pediatr Res. 2022-9

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The Lactoferrin Phenomenon-A Miracle Molecule.

Molecules. 2022-5-4

[6]
Development of Encapsulation Strategies and Composite Edible Films to Maintain Lactoferrin Bioactivity: A Review.

Materials (Basel). 2021-11-30

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Nanomaterial-Based Antifungal Therapies to Combat Fungal Diseases Aspergillosis, Coccidioidomycosis, Mucormycosis, and Candidiasis.

Pathogens. 2021-10-12

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Current applications and prospects of nanoparticles for antifungal drug delivery.

EXCLI J. 2021-3-8

[9]
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Nat Nanotechnol. 2021-3

[10]
The Toxicity of Polystyrene-Based Nanoparticles in Is Associated with Nanoparticle Charge and Uptake Mechanism.

Chem Res Toxicol. 2021-4-19

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