Biodegraded magnetosomes with reduced size and heating power maintain a persistent activity against intracranial U87-Luc mouse GBM tumors.
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.
['Alphandéry|Edouard|E|http://orcid.org/0000-0002-2952-2270', 'Idbaih|Ahmed|A|', 'Adam|Clovis|C|', 'Delattre|Jean-Yves|JY|', 'Schmitt|Charlotte|C|', 'Gazeau|Florence|F|', 'Guyot|François|F|', 'Chebbi|Imène|I|']
D000818:Animals D000970:Antineoplastic Agents D001932:Brain Neoplasms D045744:Cell Line, Tumor D002470:Cell Survival D005260:Female D006361:Heating D006801:Humans D006979:Hyperthermia, Induced D060526:Magnetic Fields D058185:Magnetite Nanoparticles D055944:Magnetosomes D042201:Magnetospirillum D051379:Mice D008819:Mice, Nude D010316:Particle Size D000068936:Theranostic Nanomedicine D014018:Tissue Distribution
U87-Luc Magnetotactic bacteria Alternating magnetic field Antitumor efficacy Chains of magnetosomes Glioblastoma Hyperthermia Magnetic hyperthermia Nanomedicine Nanooncology Nanotherapy Oncology Thermotherapy