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Synergistic dual-modified liposome improves targeting and therapeutic efficacy of bone metastasis from breast cancer.

ABSTRACT: Breast cancer frequently metastasizes to bone, where it leads to poor clinical prognosis. Due to the peculiarity of the bone microstructure, the uptake of drugs often happens at non-targeted sites, which produces a similar cytotoxicity in both cancerous and healthy cells. In this study, a rational strategy was implemented to take advantage of a combination of both an octapeptide with eight repeating sequences of aspartate (Asp₈) and folate to create a more selective and efficient drug delivery system to target cancer cells in bone tissue. Asp₈ and folate were conjugated to the distal ends of DSPE-PEG₂₀₀₀-maleimide and DSPE-PEG₂₀₀₀-amine to create DSPE-PEG₂₀₀₀-Asp₈ and DSPE-PEG₂₀₀₀-Folate, respectively, which were incorporated onto the surface of a doxorubicin (DOX)-loaded liposomes (A/F-LS). Asp₈, similar to the hydroxyapatite-binding domains of osteopontin and osteocalcin, has been used as bone-targeting moieties for exclusive delivery of drugs to bone. The folate moiety binds selectively to folate receptor-positive tumors. The dual-targeting effects were evaluated by both in vitro and in vivo experiments. By taking advantages of dual-targeting drug delivery, the dual-modified liposomal drug system could relieve pain and improve survival. Inspired by its enhanced therapeutic efficacy and low toxicity, DOX-loaded A/F-LS could serve as an effective drug system for targeted therapy of bone metastases.

SUBMITTER: Ke X

PROVIDER: S-EPMC8241154 | biostudies-literature |

REPOSITORIES: biostudies-literature

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