Lipidic Cubic-Phase Nanoparticles (Cubosomes) Loaded with Doxorubicin and Labeled with <sup>177</sup>Lu as a Potential Tool for Combined Chemo and Internal Radiotherapy for Cancers
Adrianna Cytryniak,
Ewa Nazaruk,
Renata Bilewicz,
Emilia Górzyńska,
Kinga Żelechowska-Matysiak,
Rafał Walczak,
Adam Mames,
Aleksander Bilewicz,
Agnieszka Majkowska-Pilip
Affiliations
Adrianna Cytryniak
Faculty of Chemistry, University of Warsaw, Pasteura 1 St., 02-093 Warsaw, Poland
Ewa Nazaruk
Faculty of Chemistry, University of Warsaw, Pasteura 1 St., 02-093 Warsaw, Poland
Renata Bilewicz
Faculty of Chemistry, University of Warsaw, Pasteura 1 St., 02-093 Warsaw, Poland
Emilia Górzyńska
Centre of Radiochemistry and Nuclear Chemistry, Institute of Nuclear Chemistry and Technology, Dorodna 16 St., 03-195 Warsaw, Poland
Kinga Żelechowska-Matysiak
Centre of Radiochemistry and Nuclear Chemistry, Institute of Nuclear Chemistry and Technology, Dorodna 16 St., 03-195 Warsaw, Poland
Rafał Walczak
Centre of Radiochemistry and Nuclear Chemistry, Institute of Nuclear Chemistry and Technology, Dorodna 16 St., 03-195 Warsaw, Poland
Adam Mames
Institute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka 44/52 St., 01-224 Warsaw, Poland
Aleksander Bilewicz
Centre of Radiochemistry and Nuclear Chemistry, Institute of Nuclear Chemistry and Technology, Dorodna 16 St., 03-195 Warsaw, Poland
Agnieszka Majkowska-Pilip
Centre of Radiochemistry and Nuclear Chemistry, Institute of Nuclear Chemistry and Technology, Dorodna 16 St., 03-195 Warsaw, Poland
Lipid liquid-crystalline nanoparticles (cubosomes) were used for the first time as a dual-modality drug delivery system for internal radiotherapy combined with chemotherapy. Monoolein (GMO)-based cubosomes were prepared by loading the anticancer drug, doxorubicin and a commonly used radionuclide, low-energy beta (β−)-emitter, 177Lu. The radionuclide was complexed with a long chain derivative of DOTAGA (DOTAGA-OA). The DOTAGA headgroup of the chelator was exposed to the aqueous channels of the cubosomes, while, concerning OA, the hydrophobic tail was embedded in the nonpolar region of the lipid bilayer matrix, placing the radioactive dopant in a stable manner inside the cubosome. The cubosomes containing doxorubicin and the radionuclide complex increased the cytotoxicity measured by the viability of the treated HeLa cells compared with the effect of single-drug cubosomes containing either the DOX DOTAGA-OA or DOTAGA-OA-177Lu complex. Multifunctional lipidic nanoparticles encapsulating the chemotherapeutic agent together with appropriately complexed (β−) radionuclide are proposed as a potential strategy for effective local therapy of various cancers.
