RGD-functionalized magnetosomes are efficient tumor radioenhancers for X-rays and protons

Abstract

Rationale Radiation therapy is widely used for cancer treatment but its efficacy is limited by radioresistance and by damages caused to adjacent normal tissues. Active research aims at maximizing tumor eradication while reducing side-effects with theranostic nanoparticles that act as radioenhancers in situ. Ferromagnetic materials have been identified as promising nanotools for image-guided radiotherapy. Here, we investigated the potential of RGD-tagged magnetosomes (magnetosomes@RGD), bacterial biogenic magnetic nanoparticles naturally coated by a biological membrane and genetically engineered to express a RGD peptide, as tumour enhancers to conventional radiotherapy and proton therapy. Methods The potential of native and RGD-functionalized magnetosomes to enhance the effects of ionizing radiations was assessed in a DNA fragmentation assay and in melanoma and colorectal cancer cells using in vitro clonogenic assays. The in vivo radiotherapy enhancement efficacy of the magnetosomes@RGD was explored in preclinical models of melanoma-bearing mice treated with either X-rays or protons. Results Native and RGD-tagged magnetosomes similarly enhanced radiation-induced DNA damage. On cancer cells, both magnetoprobes were able to boost the killing efficacy of radiotherapy, although to a much larger extent with the magnetosomes@RGD enhancing the mortality by 2.5 fold in melanoma cells and by 2.9 fold in colorectal cancer cells. In vivo treatment of melanomabearing mice with magnetosomes@RGD prior to X-rays led to a 65% reduction in tumor development compared to radiotherapy alone (31%). Comparatively, a more effective tumor 3 growth inhibition (77%) was observed in combining RGD-decorated nanoprobes to proton therapy. The radioenhancing potential of magnetosomes@RGD was further evidenced by the DNA damage observed in the nanoscale vicinity of magnetosomes within the treated lesions. Conclusions Our results show efficacy of magnetosomes functionalized with a RGD peptide as tumor radioenhancers to both X-rays and protons in vivo and strengthen the interest of developing biogenic magnetoparticles for multimodal nanomedicine for cancer therapy.

An automated oxystat fermentation regime for microoxic cultivation of Magnetospirillum gryphiswaldense

“…In the widely studied alphaproteobacterium Magnetospirillum gryphiswaldense each step is highly regulated by a set of more than 30 genes leading to the formation of single crystalline magnetite particles with defined size, shape and magnetic properties, which are so far unmatched by magnetic nanoparticles produced by chemical synthesis [ 4 – 7 ]. Hence, magnetosomes are of great potential in the biomedical and biotechnological field, and isolated magnetosomes were already successfully applied for cancer treatment, such as magnetic hyperthermia [ 8 – 10 ], phototherapy [ 11 ] and radiosensitization [ 12 ], as contrast agent for magnetic imaging [ 13 – 16 ] and as a tool in immune assays [ 17 ]. Furthermore, the proteinaceous membrane of magnetosomes from M. gryphiswaldense and related organisms can be functionalized by genetic or chemical coupling of additional functional moieties, such as enzymes for immobilization of enzymatic cascades [ 18 – 21 ], fluorophores, antibodies for diagnostic purposes e.g.…”

A Sensitive Magnetic Arsenite-Specific Biosensor Hosted in Magnetotactic Bacteria

“…Four plasmid constructions were built by insertion of either arsR1 or arsR= and their respective promoters followed by two different reporter genes. The gene encoding the fluorescent protein Venus was first chosen because of its small size and because it was known to be functional in MTB (33)(34)(35). However, preliminary experiments performed to measure the fluorescent signal in rich growth media, such as the one used for MSR-1, revealed a high background noise and determined that it would require additional washing to remove growth medium in order to obtain an optimal measurement.…”

Green nanomedicine: the path to the next generation of nanomaterials for diagnosing brain tumors and therapeutics?

“…The results of the study showed that the RGDmagnetosomes were able to boost the efficacy of radiotherapy to a much larger extent than native magnetosomes and that the combination of the NPs and proton therapy exceeded the efficacy of X-rays at equivalent doses while increasing secondary emission after irradiation of the magnetosomes with protons versus photons. Consequently, the results indicated the therapeutic adv antages of using functionalized magnetosomes to sensitize tumors to both X-rays and protons compared to chemically-produced NPs [106].…”