Aims and objectives
SN132D is a nanoparticle-based contrast agent which uses manganese (Mn) as paramagnetic agent.
The composition offers a slow wash out,
which enables high resolution MR imaging over a few hours after administration and accumulation in malignant tissue to enable enhanced tumor selectivity.
A thorough investigation of SN132D has been performed:
To analyze the relaxometric behavior of SN132D and to investigate the relationship with the microenvironment in which the nanoparticles distribute once administered in vivo
To show efficacy of SN132D in breast cancer tumor models in...
Methods and materials
Nanoparticle synthesis
SN132D nanoparticles contains a core prepared from monomer precursor (Fig. 1A – compound 1) which is coated with a dipodal coating precursor (Fig. 1A – compound 2).
Mn ions,
in the form of MnCl2,
was loaded into the coated nanoparticles in a phosphorus to Mn ratio of 7.
The nanoparticles between 70 and 10 kDa were collected by tangential flow filtration.
The diafiltered material was then concentrated using a 10 kDa filter and further formulated with CaCl2 and MnCl2 to be in electrolyte...
Results
SN132D is a Mn-based contrast agent composed of nanoparticles with high relaxivity
SN132D is a Mn-containing nanoparticle contrast agent for tumor selective MRI.
SN132D contains a polymeric core with Mn(II)ions chelated to phosphonate groups.
A coating layer of covalently attached-PEG-polymers covers the core (Fig.
1B).
The coating layer prevents aggregation,
reduce binding to plasma proteins and makes the nanoparticle immunogenically inert [1].
The phosphonates are efficient chelators with an average of 14 Mn(II)ions bound to each particle,
and a chelating strength of the same order...
Conclusion
SN132D showed improved CNRs in the 4T1 cancer model with an extended time window for up to 2 - 4 hours after administration.
Toxicology and safety studies of SN132D in rat and minipig showed a favourable safety profile and NOAEL could be identified in both species.
Observed preclinical toxicity at high doses is considered related to Mn.
In-vitro cytotoxicity in all cell lines investigated were due to Mn-induced apoptosis.
The SN132D nanoparticle does not bind irreversibly to plasma proteins,
induce complement activation in vitro in...
Personal information
M.
Hansen,
CEO,
PhD
Spago Nanomedical AB,
Sweden
Scheelevägen 22
SE - 223 63 Lund
Sweden
Phone: +46767764294
e-mail:
[email protected]
www.spagonanomedical.se
References
[1] Eliana Gianolio,
Sania Bäckström,
Rodrigo M Petoral Jr,
Anders Olsson,
Silvio Aime,
Oskar Axelsson (2018).
Manganese-based Nanoparticles as high relaxivity MRI contrast agent.
Manuscript accepted for publication in 'European Journal of Inorganic Chemistry',
doi: 10.1002/ejic.201801472
[2]Eriksson P-O,
Aaltonen E,
Petoral R Jr,
Lauritzson P,
Miyazaki H,
et al.
(2014) Novel Nano-Sized MR Contrast Agent Mediates Strong Tumour Contrast Enhancement in an Oncogene-Driven Breast Cancer Model.
PLoS ONE 9(10): e107762.
doi:10.1371/journal.pone.0107762
[3]Pulaski BA and Ostrand-Rosenberg S (2001) Mouse 4T1 breast tumour model.
Curr Protoc Immunol....