New radio-nano-medicine strategies for targeting stem-like cancer cells in glioblastoma
Sehedic, D.; Hindre, F.; Garcion, E.; Mougin-Degraeff, M.; Davodeau, F.
WIPR 2013 - Radiopharmaceuticals: from research to industry - Book of abstracts2015
WIPR 2013 - Radiopharmaceuticals: from research to industry - Book of abstracts2015
AbstractAbstract
[en] Full text of publication follows. Although only palliative, external beam radiation remains to date the standard treatment of dramatic brain glioblastoma (GBM). Radiotherapy effectiveness is indeed largely limited by resistance mechanisms combining intrinsic properties of tumour cells to the influence of the microenvironment in which they develop (e.g. hypoxia). The recent discovery of stem-like cancer cells (SLCC) in GBM supports the presumption that the failure of conventional antitumor strategies could be attributed to a problem of target cells. Thus, the present work deals with the development of a new-targeted internal radiotherapy to radio-resistant SLCC through the use of nano-carriers loaded with α- or β- radiation emitters. As CXCR4 receptor has been associated with radio-resistance and with SLCC occurrence, we focused on the targeting of these proteins in a human GBM models known to express it: A172. We primarily developed 50 nm lipid nanocapsules (LNCs) functionalized with monoclonal antibodies (mAbs) directed against CXCR4 (or iso-type control) [Ref.1]. LNCs will then be combined to 188Re (beta emitter) and 211At (α-emitter) for further evaluation. By using blocking antibodies, our investigations merged the interest of targeting SLCC associated epitopes to the one of inhibiting CXCR4 signaling pathways to overcome radioresistance. In line with this, by using immunofluorescence flow cytometry, we found that CXCR4 expression is correlated with radiation doses: we found 41% expression when are radiated at 32 Gy versus 10% expression when they are radiated at 0 Gy. Finally, new encapsulation of 125I (β-emitter and halogen), which will help for the development of 211At (halogen), has been developed. Preliminary results show a relatively stable SIB encapsulation over time in different medium. Efficacies of β- versus α-nano-carrier based radio-therapies will then be compared in vivo after ortho-topic implantation of human GBM cells in immuno deprived SCID mice and loco-regional infusion of the treatment. Reference: Ref.1: Bourseau-Guilmain, E.; Bejaud, J.; Griveau, A.; Lautram, N.; Hindre, F. et al. Development and characterization of immuno nano-carriers targeting the cancer stem cell marker AC133. International Journal of Pharmaceutics. (authors)
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Laboratoire Subatech, 4 rue Alfred Kastler, 44307 Nantes (France); 171 p; 2015; p. 123; WIPR 2013: Radiopharmaceuticals - from research to industry; Nantes (France); 9-12 Jul 2013; Available in abstract form only, full text entered in this record; 1 ref.
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ALPHA DECAY RADIOISOTOPES, ASTATINE ISOTOPES, BETA DECAY RADIOISOTOPES, BETA-MINUS DECAY RADIOISOTOPES, DAYS LIVING RADIOISOTOPES, DISEASES, ELECTRON CAPTURE RADIOISOTOPES, HEAVY NUCLEI, HOURS LIVING RADIOISOTOPES, INTERMEDIATE MASS NUCLEI, INTERNAL CONVERSION RADIOISOTOPES, IODINE ISOTOPES, ISOMERIC TRANSITION ISOTOPES, ISOTOPES, MEDICINE, MINUTES LIVING RADIOISOTOPES, NEOPLASMS, NERVOUS SYSTEM DISEASES, NUCLEAR MEDICINE, NUCLEI, ODD-EVEN NUCLEI, ODD-ODD NUCLEI, RADIOISOTOPES, RADIOLOGY, RHENIUM ISOTOPES, THERAPY
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