Lipidic Cubic-Phase Nanoparticles (Cubosomes) Loaded with Doxorubicin and Labeled with 177Lu as a Potential Tool for Combined Chemo and Internal Radiotherapy for Cancers

Abstract

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.

Potentiating the Cytotoxic Activity of a Novel Simvastatin-Loaded Cubosome against Breast Cancer Cells: Insights on Dual Cell Death via Ferroptosis and Apoptosis

“…Compared with liposomes, cubosomes exert a higher stability and a larger ratio of bilayer area to particle volume, which facilitates the interaction with the lipid bilayer structure of cells. 23 Interestingly, cubosomes maintain a stable three-dimensional structure under a range of physiologically relevant conditions which provide a highly efficient penetration power in cancerous cells. 24 Therefore, in the present study, we formulated a novel biocompatible SIM-loaded cubosome nanoparticle (SIM-CB), in attempt to enhance the anticancer potential of SIM, and maximize the advantage of SIM lipophilicity as a promising ferroptosis inducer.…”

Schiff-Linked PEGylated Doxorubicin Prodrug Forming pH-Responsive Nanoparticles With High Drug Loading and Effective Anticancer Therapy

“…Therefore, significant progress has been made towards the fabrication of ideal DOX delivery system with improved drug utilization at the action sites and reduced side effects in non-target tissues. Although the liposomal formulations of DOX have been approved for clinical use and many polymeric nanoparticles loading DOX molecules are being evaluated in clinical trials (14)(15)(16)(17)(18), these DOX-loaded nanocarriers have some inherent drawbacks like low drug loading, premature burst release and inactive carriers to patients, which may ascribe to the high polarity and hydrophilicity of DOX molecules. To overcome this unintended and undesirable leakage, chemically-linked drug carriers offer an alternative for the effective anti-tumor treatment.…”

Advances of Nanomedicine in Radiotherapy

“…Cytryniak et al loaded doxorubicin and radionuclide 177 Lu into the monoolein (GMO)-based lipid liquid-crystalline nanoparticles (cubosomes) to form a novel complex (DOTAGA-OA-177 Lu). This complex had strong structural stability, and compared with pure nuclide therapy, it had stronger cell-killing effect in vitro [60].…”