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用于在交变磁场或超声应用下于 45±1°C 有效破坏肿瘤细胞的冷冻保护非致热等渗磁小体链的稳定药物组合物。

Stable pharmaceutical composition of cryo-protected non-pyrogenic isotonic chains of magnetosomes for efficient tumor cell destruction at 45 ± 1 °C under alternating magnetic field or ultrasound application.

机构信息

Nanobacterie SAS, 36 boulevard Flandrin, 75116, Paris, France.

Institut de minéralogie de physique des matériaux et de cosmochimie, Sorbonne Université UMR 7590 CNRS, Université Pierre et Marie Curie, Muséum National d'Histoire Naturelle. 4 Place Jussieu, 75005 Paris, France.

出版信息

Nanoscale. 2024 Oct 17;16(40):18984-18997. doi: 10.1039/d4nr02284j.


DOI:10.1039/d4nr02284j
PMID:39297787
Abstract

We report a method to prepare biocompatible, stable, and highly pure iron oxide nano-minerals by following the steps consisting of: (i) amplifying magnetotactic bacteria in non-toxic minimal growth media; (ii) extracting magnetosomes from magnetotactic bacteria under alkaline lysis; (iii) heating magnetosomes above 400 °C to yield sterile magnetosome minerals, M-uncoated, devoid of active non-denatured bacterial organic material; (iv) coating M-uncoated with biocompatible carboxymethyl-dextran (CMD) compounds to yield stable M-CMD; (v) adding 5% sorbitol to M-CMD; and (vi) lyophilizing these mixtures, resulting in formulated nano-minerals in powder forms, designated as (M-CMD). The long-term stability of the final products is demonstrated by re-suspending (M-CMD) in water after 12 months of storage, and by showing that these formulated magnetosomes have preserved their stability in suspension, chain arrangement, carbon content, surface charge, and surface composition. Furthermore, the formulation is optimized to yield an isotonic magnetosome suspension with an osmolality of between 275 and 290 mOsm kg HO upon reconstitution. On one hand, these formulated magnetosomes are fully biocompatible, sterile, non-pyrogenic, and non-cytotoxic towards 3T3, L929, and V79 healthy cells up to 1 mg mL NP concentration iron. On the other hand, when they are brought into the presence of PC3-Luc prostate tumor cells and heated moderately at ∼41-46 °C for 20-30 minutes under low-intensity ultrasound or alternating magnetic field conditions, they efficiently destroy these tumor cells.

摘要

我们报告了一种通过以下步骤制备生物相容性、稳定且高纯度的氧化铁纳米矿物质的方法:(i)在无毒的最小生长培养基中扩增趋磁细菌;(ii)在碱性裂解下从趋磁细菌中提取磁小体;(iii)将磁小体加热至 400°C 以上,得到无菌的磁小体矿物质,即 M-无涂层,没有活性的未变性细菌有机物质;(iv)用生物相容性的羧甲基-葡聚糖(CMD)化合物对 M-无涂层进行涂层,得到稳定的 M-CMD;(v)向 M-CMD 中添加 5%山梨醇;(vi)对这些混合物进行冻干,得到粉末状的配方纳米矿物质,命名为(M-CMD)。通过在储存 12 个月后将(M-CMD)重新悬浮在水中,以及通过表明这些配方化的磁小体在悬浮液中、链排列、碳含量、表面电荷和表面组成方面保持稳定,证明了最终产物的长期稳定性。此外,通过优化配方,可得到渗透压为 275 至 290 mOsm kg HO 的等渗磁小体悬浮液。一方面,这些配方化的磁小体完全生物相容、无菌、无热原且对 3T3、L929 和 V79 健康细胞无细胞毒性,浓度高达 1 mg mL NP 铁。另一方面,当它们被引入 PC3-Luc 前列腺肿瘤细胞并在低强度超声或交变磁场条件下温和加热至约 41-46°C 20-30 分钟时,它们能够有效地破坏这些肿瘤细胞。

相似文献

[1]
Stable pharmaceutical composition of cryo-protected non-pyrogenic isotonic chains of magnetosomes for efficient tumor cell destruction at 45 ± 1 °C under alternating magnetic field or ultrasound application.

Nanoscale. 2024-10-17

[2]
Non-pyrogenic highly pure magnetosomes for efficient hyperthermia treatment of prostate cancer.

Appl Microbiol Biotechnol. 2023-2

[3]
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[5]
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[6]
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[7]
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[9]
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[10]
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