BACKGROUND An important but rarely addressed question in nano-therapy is to know whether bio-degraded nanoparticles with reduced sizes and weakened heating power are able to maintain sufficient anti-tumor activity to fully eradicate a tumor, hence preventing tumor re-growth. To answer it, we studied magnetosomes, which are nanoparticles synthesized by magnetotactic bacteria with sufficiently large sizes (~ 30 nm on average) to enable a follow-up of nanoparticle sizes/heating power variations under two different altering conditions that do not prevent anti-tumor activity, i.e. in vitro cellular internalization and in vivo intra-tumor stay for more than 30 days. RESULTS When magnetosomes are internalized in U87-Luc cells by being incubated with these cells during 24 h in vitro, the dominant magnetosome sizes within the magnetosome size distribution (DMS) and specific absorption rate (SAR) strongly decrease from DMS ~ 40 nm and SAR ~ 1234 W/gFe before internalization to DMS ~ 11 nm and SAR ~ 57 W/gFe after internalization, a behavior that does not prevent internalized magnetosomes to efficiently destroy U87-Luc cell, i.e. the percentage of U87-Luc living cells incubated with magnetosomes decreases by 25% between before and after alternating magnetic field (AMF) application. When 2 µl of a suspension containing 40 µg of magnetosomes are administered to intracranial U87-Luc tumors of 2 mm3 and exposed (or not) to 15 magnetic sessions (MS), each one consisting in 30 min application of an AMF of 27 mT and 198 kHz, DMS and SAR decrease between before and after the 15 MS from ~ 40 nm and ~ 4 W/gFe down to ~ 29 nm and ~ 0 W/gFe. Although the magnetosome heating power is weakened in vivo, i.e. no measurable tumor temperature increase is observed after the sixth MS, anti-tumor activity remains persistent up to the 15th MS, resulting in full tumor disappearance among 50% of treated mice. CONCLUSION Here, we report sustained magnetosome anti-tumor activity under conditions of significant magnetosome size reduction and complete loss of magnetosome heating power.

中文翻译：

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生物降解的磁小体具有较小的尺寸和加热功率，可保持对颅内 U87-Luc 小鼠 GBM 肿瘤的持续活性。

背景技术纳米治疗中一个重要但很少被解决的问题是了解尺寸减小和加热功率减弱的生物降解纳米颗粒是否能够保持足够的抗肿瘤活性以完全根除肿瘤，从而防止肿瘤再生长。为了回答这个问题，我们研究了磁小体，它是由趋磁细菌合成的纳米颗粒，具有足够大的尺寸（平均约 30 nm），以便能够在两种不同的改变条件下跟踪纳米颗粒尺寸/加热功率的变化，而不会妨碍抗-肿瘤活性，即体外细胞内化和体内瘤内停留超过30天。结果当磁小体通过在体外与 U87-Luc 细胞一起孵育 24 小时而被内化时，磁小体尺寸分布 (DMS) 和比吸收率 (SAR) 内的主要磁小体尺寸从 DMS ~ 40 nm 和 SAR 急剧下降内化至 DMS 之前约为 1234 W/gFe 内化后约为 11 nm，SAR 约为 57 W/gFe，这种行为不会阻止内化磁小体有效破坏 U87-Luc 细胞，即与磁小体一起孵育的 U87-Luc 活细胞的百分比应用交变磁场 (AMF) 之前和之后减少了 25%。当将 2 µl 含有 40 µg 磁小体的悬浮液施用至 2 mm3 的颅内 U87-Luc 肿瘤并暴露（或不暴露）15 次磁力疗程 (MS) 时，每一次包括 30 分钟应用 27 mT 的 AMF 和198 kHz、DMS 和 SAR 在 15 MS 之前和之后从 ~ 40 nm 和 ~ 4 W/gFe 下降到 ~ 29 nm 和 ~ 0 W/gFe。尽管磁小体加热能力在体内减弱，即在第六次MS后没有观察到可测量的肿瘤温度升高，但抗肿瘤活性仍然持续到第15次MS，导致50%的治疗小鼠的肿瘤完全消失。结论在这里，我们报告了在磁小体尺寸显着减小和磁小体加热功率完全丧失的条件下持续的磁小体抗肿瘤活性。