Perpustakaan Digital ITB

In the context of cancer treatment, gold nanoparticles (AuNPs) are considered as very promising radiosensitizers. Here, well- de fi ned polymer-grafted AuNPs were synthesized and studied under gamma irradiation to better understand the involved radiosensitizing mechanisms. First, various water-soluble and well-de fi ned thiol-function- alized homopolymers and copolymers were obtained through atom transfer radical polymerization. They were then used as ligands in the one-step synthesis of AuNPs, which resulted in stable hybrid metal ? polymer nanoparticles. Second, these nano-objects were irradiated in solution by ? rays at di ff erent doses. Structures were fully characterized through size exclusion chromatography, small-angle X-ray scattering, and small-angle neutron scattering measurements, prior to and after irradiation. We were thus able to quantify and to localize radiation impacts onto the grafted polymers, revealing the production sites of reactive species around AuNPs. Both external and near-surface scissions were observed. Interestingly, the ratio between these two e ff ects was found to vary according to the nature of polymer ligands. Medium-range and long-distance dose enhancements could not be identi fi ed from the calculated scission yields, but several mechanisms were considered to explain high yields found for near-surface scissions. Then cytotoxicity was shown to be equivalent for both nonirradiated and irradiated polymer-grafted NPs, which suggested that released polymer fragments were nontoxic. Finally, the potential to add bioactive molecules such as anticancer drugs has been explored by grafting doxorubicin onto the polymer corona. This may lead to nano-objects combining both radiosensitization and chemotherapy e ff ects. This work is the fi rst one to study in details the impact of radiation on radiosensitizing nano-objects combining physical, chemical, and biological analyses.